WO2025083216A1 - Antibodies specific for the spike protein of sars cov-2 coronavirus - Google Patents

Abstract

The present invention relates to antibodies capable of binding to the spike protein of coronavirus SARS-CoV-2, and methods and uses thereof in the prevention, treatment and/or diagnosis of coronavirus infections, and diseases and/or complications associated with coronavirus infections, including COVID-19.

Description

ANTIBODIES Field of invention The invention relates to antibodies useful for the prevention, treatment and/or diagnosis of coronavirus infections, and diseases and/or complications associated with coronavirus infections, including COVID-19.

of the invention A severe viral acute respiratory syndrome named COVID-19 was first reported in Wuhan, China in December 2019. The virus rapidly disseminated globally leading to the pandemic with >200M confirmed infections and over 4.4M deaths in 12 months. The causative agent, SARS-CoV-2, is a beta coronavirus, related to SARS-CoV-1 and MERS coronaviruses, which both cause severe respiratory syndromes. The majority of the human population is believed to have been exposed to SARS- CoV-2, by natural infection (771 million cases and 7 million deaths confirmed as of 27/9/23, but the actual numbers are likely much higher), and/or vaccination, often on multiple occasions. This herd immunity has put the SARS-CoV-2 genome under huge selective pressure to evade pre-existing immune responses, hence the abundance of variants. It is therefore an object of the invention to identify further and improved antibodies useful for preventing, treating and/or diagnosing coronavirus infections, and diseases and/or complications associated with coronavirus infections, including COVID-19. of the invention The inventors identified 10 human monoclonal antibodies (mAbs) recognizing the spike protein of SARS-CoV-2, and they are listed in Table 1 and are also referred to as the XBB antibodies herein. These antibodies showed potent neutralisation activity against SARS-CoV-2 (e.g. see Figure 4 and Table 5), in particular, against the BA.2.86 variant, which is a recently described sub-lineage of SARS-CoV-2 Omicron, comprising a large number of mutations in the spike gene (e.g. see Figure 1A). BA.2.86 originated from BA.2 and is distinct from the XBB variants currently responsible for most infections. The global spread and plethora of mutations in BA.2.86 has caused concern that it may possess greater immune evasive potential, leading to a new wave of infection. Furthermore, the inventors identified that SARS-CoV-2 may be under immune selective pressure to acquire mutations in a region in the spike protein that contains amino acid residues at positions 455 and 456 (numbering relative to the spike protein of the hCoV-19/Wuhan/WIV04/2019 strain). This was evident from the blocking or severely impairment of activity of 7 out of 10 potent XBB antibodies when residues 455 and 456 were mutated, e.g. in XBB.1.5.10, AG.1.5 (F456L) and XBB.1.5.70 (L455F and F456L) (see Table 5 and Figure 4). Therefore, antibodies that target this epitope would result in a resilient antibody. Accordingly, the invention provides an antibody capable of binding to the spike protein of coronavirus SARS-CoV-2, wherein the antibody comprises the six CDRs of antibody XBB-9, or of any one of the antibodies in Tables 1 to 4. The invention also provides an antibody capable of binding to the spike protein of coronavirus SARS-CoV-2, wherein the antibody comprises CDRH1, CDRH2 and CDRH3, from a first antibody in Table 1 and CDRL1, CDRL2 and CDRL3 from a second antibody in Table 1, with the proviso that the first antibody and the second antibody are different. The invention also provides one or more polynucleotides encoding an antibody of the invention, such as a first polynucleotide encoding the heavy chain variable domain of the antibody and a second polynucleotide encoding the light chain variable domain of the antibody. The invention also provides one or more vectors comprising the one or more polynucleotides of the invention. The invention also provides a host cell comprising the one or more vectors of the invention. The invention also provides a method for producing an antibody that is capable of binding to the spike protein of coronavirus SARS-CoV-2, the method comprising culturing a host cell of the invention and isolating the antibody from said culture. The invention also provides a method of generating an antibody capable of binding to the spike protein of SARS-CoV-2, comprising raising an antibody against an epitope comprising amino acid residues at positions 455 and 456 in the spike protein of coronavirus SARS-CoV-2, relative to the spike protein of the hCoV- 19/Wuhan/WIV04/2019 strain, optionally wherein the raising of the antibody is performed by hybridoma technology, phage display technology or by immunizing an animal with the modified spike protein. The invention also provides an antibody obtained or obtainable by said method. The invention also provides an antibody that is capable of binding to an epitope comprising amino acid residues at positions 455 and 456 in the spike protein of coronavirus SARS-CoV-2, relative to the spike protein of the hCoV- 19/Wuhan/WIV04/2019 strain; and/or capable of binding to the same epitope on the spike protein as, or competes with, antibody XBB-9. The invention also provides a pharmaceutical composition comprising: (a) one or more antibody of the invention, and (b) at least one pharmaceutically acceptable diluent or carrier. The invention also provides a combination of antibodies comprising two or more antibodies of the invention. The invention also provides an antibody or a pharmaceutical composition of the invention for use in a method for treatment of a human or animal by therapy. The invention also provides an antibody or a pharmaceutical composition of the invention for use in a method of treating or preventing coronavirus infection, or a disease or complication associated with coronavirus infection The invention also provides a method of treating or preventing coronavirus infection, or a disease or complication associated with coronavirus infection in a subject, comprising administering a therapeutically effective amount of an antibody or a pharmaceutical composition of the invention to said subject. The invention also provides a method of identifying the presence of coronavirus, or a protein fragment thereof, in a sample, comprising: (i) contacting the sample with an antibody of the invention, and (ii) detecting the presence or absence of an antibody-antigen complex, wherein the presence of the antibody-antigen complex indicates the presence of coronavirus, or a fragment thereof, in the sample. The invention also provides a method of treating or preventing coronavirus infection, or a disease or complication associated therewith, in a subject, the method comprising identifying the presence of coronavirus according to said method in a sample, and treating the subject with an antibody of the invention, an anti-viral drug or an anti-inflammatory agent. The invention also provides the use of an antibody or a pharmaceutical composition of the invention for preventing, treating and/or diagnosing coronavirus infection, or a disease or complication associated therewith. The invention also provides the use of an antibody or a pharmaceutical composition of the invention for the manufacture of a medicament for treating or preventing coronavirus infection, or a disease or complication associated therewith. Brief description of the figures Figure 1. Sequence changes in BA.2.86 compared to other Omicron sub- lineages. (A) Sequence alignments of BA.2.86 RBD with Omicron sub-lineages BA.1, BA.2, BA.4/5, XBB.1.5, XBB.1.5.10, and XBB.1.5.70. Surface representation of (B) BA.2.86 mutations shown on BA.2. (C) XBB.1.5 mutations on BA.2. Mutations in common are coloured in magenta, further mutations in BA.2.86 and XBB.1.5 in cyan, and V483 deletion in BA.2.86 in green. If there 2 letters after the residue number in the labels, the first letter indicates the residue type for BA.2 and the second BA.2.86 or XBB.1.5. (D) Phylogenetic tree generated by aligning spike sequences of the SARS-CoV-2 variants. Figure 2. Pseudoviral neutralization assays of BA.2.86 by vaccine and infected serum samples. (A-F) Geometric mean FRNT50 values for the indicated viruses using serum obtained from vaccinated volunteers 18 months (n=17) (A) after a third dose of Pfizer BNT162b2 or Moderna vaccine, and 6 months after a fourth bivalent vaccine dose (n=23) (B). (C-E) Serum from vaccinees suffering breakthrough infections by BA.2 (n=19), BA.4/5 (n=11) and a set of samples collected following vaccine breakthrough infections in the last year (n=19). (F) A composite figure for the geometric means of all serum samples against selected Omicron sublineages. The Wilcoxon matched-pairs signed rank test was used for the analysis and two-tailed P values were calculated. (G) Antigenic map showing BA.2.86 in the context of the positions of previous lineages including several Omicron related sub-lineages calculated from pseudovirus neutralisation data. The distance between two positions is proportional to the reduction in neutralisation titre when one of the corresponding strains is challenged with serum derived by infection by the other. The inventors have previously described the method (Huo et al., 2023, Cell Rep 42, 111903), however whilst in previous reports the inventors generated a 3D map here the inventors were able to describe the map in 2D with minimal impact on the target function. An approximate scale bar is shown. Figure 3. Pseudoviral neutralization assays using BA.2 specific monoclonal antibodies. (A) Heatmap of BA.2.86 IC50 neutralization titres of 25 potent human mAbs made following BA.2 infection, compared to neutralization titres against Victoria and BA.2. The likely BA.2.86 mutations leading to loss of activity in BA.2.86 for each mAb are indicated in the final column. (B) BA.2 mAb binding positions (blue spheres) mapped on RBD surface by BLI competition measurements and structure determinations. RBD shown in grey surface representation with BA.2.86 mutation sites coloured in magenta. Figure 4 Neutralization curves for XBB.1.5 RBD-specific mAbs. XBB specific mAb isolated from breakthrough infection with recent variants. (A) Titration curves for BA.2.86 are compared with BA.2, BA.4/5, XBB.1.5, XBB.1.5.10 and XBB.1.5.70. IC50 titres are shown as a heatmap in (B). (C) Surface representation of RBD with ACE2 footprint coloured in green and the sites of mutations L455F and F456L highlighted in red (F456L in XBB.1.5.10, L455F + F456L in BA.1.5.70). (D) Heatmap of IC50 neutralization titres of mAbs developed for clinical use. (E) Binding pose of S309 (sotrovimab) and it’s interactions with K356. (F) Measurement of the affinity of ACE2 with BA.2.86, XBB.1.5 and Beta RBDs by surface plasmon resonance, titration curves for ACE2 flowed over the indicated immobilized RBDs are shown and together with the calculated KD values. (G) Comparison of ACE2/RBD affinities for RBDs from different SARS-CoV-2 variants. Figure 5. Structure of BA.2.86 ACE2 complex. (A) Binding pose of ACE2 (green) to BA.2.86 RBD (grey) compared with binding pose of ACE2 (pale cyan) to Wuhan (left panel) and BA.2.75 (middle panel) RBD (pink). The right panel shows loss of direct contacts of ACE2 to residue 486 due to F486P mutation in BA.2.86 RBD. (B) Structural differences at left shoulder between BA.2.86 (grey) and BA.2.75 (pink) RBDs due to V483 deletion in BA.2.86. (C) Electrostatic surfaces of ACE2-RBD interface. Figure 6. Structures of Delta-RBD/XBB-2, delta-RBD/XBB-6 and BA.2.86- RBD/XBB-7 complexes. (A), (B) and (C) Binding pose of XBB-2, XBB-6 and XBB-7 viewed from front (left panel) and back (right panel) of the RBD respectively. Only VH (red) and VL (blue) domains of the Fab are shown as ribbons for clarity. RBD is drawn as grey surface representation with mutation sites common to XBB.1.5 and BA.2.86 highlighted in magenta, different or additional mutation sites in BA.2.86 in cyan. (D) Positions of XBB-2 CDRs which have direct contacts (≤ 4.0 Å) with RBD. (E) Details of XBB-2 and RBD interactions. The side chains of the RBD, Fab HC and LC are shown as grey, red and blue sticks, respectively. The yellow broken bonds represent hydrogen bonds or salt bridges. (F) Position of XBB-6 CDRs. (G) Structural changes of RBD left shoulder (grey) upon binding of XBB-6 (red) compared to the RBD (teal) bound with XBB-2 (brown). (H) Details of XBB-6 and RBD interactions. (I) Positions of XBB-7 CDRs which have direct contacts with the RBD. (J) structural changes of BA.2.86 RBD (grey) due to deletion of V483 compared with XBB-2 bound delta-RBD (teal). (K) Details of XBB-7 and RBD interactions. The drawing style and colour scheme in (H) and (K) are as in (E). Figure 7. BA.2.86 mutations which knock out structurally known BA.2 mAbs. (A)-(E) Binding mode and interactions to residues which are mutated in BA.2.86 for BA2- 7, BA2-10, BA2-13, BA2-23 and BA2-36 respectively. Fab heavy chains are shown in red, light chains in blue. RBD shown as grey surface with BA.2.86 mutation site in cyan. Side chains are shown as grey, red and blue sticks for RBD, Fab heavy chain and light chain respectively. Detailed description of the invention Antibodies of the invention An antibody of the invention specifically binds to the spike protein of SAR-CoV-2. In particular, it specifically binds to the S1 subunit of the spike protein, such as the receptor binding domain (RBD). An antibody of the invention may be an antibody from or derived from any of the antibodies listed in Table 1. Table 1 lists 10 individual antibodies that were identified from recovered BA.4, BA.5.1 or XBB.1.5 SARS-CoV-2 infected patients. Table 1 also lists the SEQ ID NOs for the heavy chain variable domain and light chain variable domain nucleotide and amino acid sequences, and the complementarity determining regions (CDRs) of the variable domains, of each of the antibodies. An antibody of the invention may comprise all six CDRs of an antibody in Table 1. The antibody may comprise a heavy chain variable domain comprising or consisting of an amino acid sequence having at least 80% sequence identity, such as at least 90%, at least 95%, at least 96%, at least 97%, at least 98%, at least 99% or 100% sequence identity, to the heavy chain variable domain of an antibody in Table 1. The antibody may comprise a light chain variable domain comprising or consisting of an amino acid sequence having at least 80% sequence identity, such as at least 90%, at least 95%, at least 96%, at least 97%, at least 98%, at least 99% or 100% sequence identity, to the light chain variable domain of an antibody in Table 1. The antibody may comprise a heavy chain variable domain and a light chain variable domain comprising or consisting of an amino acid sequence having at least 80% sequence identity, such as at least 90%, at least 95%, at least 96%, at least 97%, at least 98%, at least 99% or 100% sequence identity, to the heavy chain variable domain and light chain domain, respectively, of an antibody in Table 1. The antibody may comprise mutations in the framework regions of the variable domains compared to the antibody in Table 1. For example, the antibody may comprise a heavy chain variable domain comprising the CDRH1, CDRH2 and CDRH3 of an antibody in Table 1, and a light chain variable domain comprising the CDRL1, CDRL2 and CDRL3 of the antibody in Table 1, wherein the heavy chain variable domain and the light chain variable domain comprises or consists of an amino acid sequence having at least 80% sequence identity, such as at least 90%, at least 95%, at least 96%, at least 97%, at least 98%, at least 99% or 100% sequence identity, to the heavy chain variable domain and light chain variable domain, respectively of the antibody in Table 1. The antibody may be any one of the antibodies in Table 1. The antibody in Table 1 may be selected from the group consisting of XBB-2, XBB-4, XBB-7, XBB-8 and XBB-9. These antibodies were surprisingly found to cross neutralise pseudoviral constructs of the SARS-CoV-2 variant strains BA.2, BA.4/BA.5, XBB1.5, XBB.1.5.10, XBB.1.5.70, BA.2.86, BQ.1.1 and BQ.1.1+A475V. For example, the antibody in Table 1 may be selected from the group consisting of XBB-2, XBB-7, XBB-8 and XBB-9, all of which showed potent neutralization effects (IC50 < 1μg/ml) that were broadly effective against these strains. For example, the antibody in Table 1 may be selected from the group consisting of XBB-2, XBB-7, XBB-8 and XBB-9, all of which showed potent neutralization effects (IC50 < 1μg/ml) that were broadly effective against these strains. For example, the antibody in Table 1 may be selected from the group consisting of XBB-7 and XBB-9, both of which showed potent neutralization effects (IC50 < 0.5 μg/ml) that were broadly effective against these strains. For example, the antibody in Table 1 may be XBB-9, which provided potent neutralization effects (IC50 < 50 ng/ml) that were broadly effective against these strains. The antibody in Table 1 may be selected from the group consisting of XBB-1, XBB-2, XBB-3, XBB-4, XBB-6, XBB-8, XBB-9 and XBB-10. These antibodies showed potent cross neutralisation (IC50 < 50 ng/ml) of the SARS-CoV-2 variant strains, except for XBB.1.5.10 and XBB.1.5.70, which contain mutations at residues 455 and 456 in the spike protein (numbering relative to the spike protein of the hCoV-19/Wuhan/WIV04/2019 strain). The antibody in Table 1 may be selected from the group consisting of XBB-2, XBB-4, XBB-7, XBB-8 and XBB-9. These antibodies retained potent neutralisation effects (IC50 < 1μg/ml) against SARS-CoV-2 variant strains in which the residues at positions 455 and 456 have been mutated (numbering relative to the spike protein of the hCoV-19/Wuhan/WIV04/2019 strain), e.g. strains XBB.1.5.10 and XBB.1.5.70. For example, the antibody in Table 1 may be selected from the group consisting of XBB-4, XBB-7 and XBB-9, all of which retained potent neutralization effects (IC50 < 0.5 μg/ml) against SARS-CoV-2 variant strains in which positions 455 and 456 have been mutated (numbering relative to the spike protein of the hCoV-19/Wuhan/WIV04/2019 strain), e.g. strains XBB.1.5.10 and XBB.1.5.70. For example, the antibody in Table 1 may be XBB-9. The neutralisation activity of XBB-9 was not affected by mutations at positions 455 and 456 (e.g. in strains XBB.1.5.10 and XBB.1.5.70). The antibody in Table 1 may be XBB-9. Hence, an antibody of the invention may comprise the six CDRs of antibody XBB-9, which are CDRH1, CDRH2, CDRH3, CDRL1, CDRL2 and CDRL3 having the amino acid sequences specified in SEQ ID NOs: 85, 86, 87, 88, 89 and 90, respectively. The antibody of the invention may comprise a heavy chain variable domain comprising or consisting of an amino acid sequence having ≥80%, ≥90%, ≥95%, ≥96%, ≥97%, ≥98%, ≥99% or 100% sequence identity to the heavy chain variable domain of antibody XBB-9 (i.e. SEQ ID NO: 82). The antibody of the invention may comprise a light chain variable domain comprising or consisting of an amino acid sequence having ≥80%, ≥90%, ≥95%, ≥96%, ≥97%, ≥98%, ≥99% or 100% sequence identity to the light chain variable domain of antibody XBB-9 (i.e. SEQ ID NO: 84). The antibody of the invention may comprise a heavy chain variable domain and a light chain variable domain comprising or consisting of an amino acid sequence having ≥80%, ≥90%, ≥95%, ≥96%, ≥97%, ≥98%, ≥99% or 100% sequence identity to the heavy chain variable domain and light chain variable domain, respectively, of antibody XBB-9 (i.e. SEQ ID NOs: 82 and 84, respectively). The antibody of the invention may be a full- length antibody, for example, the antibody may comprise a heavy chain variable domain and a light chain variable domain as set out in SEQ ID NOs: 82 and 84, respectively, and a constant region, such as an IgA, IgD, IgE, IgG (IgG1, IgG2, IgG3 or IgG4) or IgM constant region. The heavy chain domain of XBB-9 is derived from a IGHV3-53 v-region, and the inventors have previously demonstrated that switching of the heavy chains and light chains between antibodies derived from IGHV3-53 v-region (e.g. XBB-2 or XBB-8) and IGHV3- 66 (e.g. XBB-3 or XBB-10) results in an antibody that is particularly useful with the invention (explained further below). Hence, an antibody of the invention may comprise the heavy chain of XBB-9, and not the light chain of XBB-9. For example, the antibody may comprise a CDRH1, CDRH2 and CDRH3 having the amino acid sequences specified in SEQ ID NOs: 85, 86 and 87, respectively. The antibody may comprise a heavy chain variable domain comprising or consisting of an amino acid sequence having ≥80%, ≥90%, ≥95%, ≥96%, ≥97%, ≥98%, ≥99% or 100% sequence identity to the heavy chain variable domain of antibody XBB-9 (i.e. SEQ ID NO: 82). The antibody may comprise a heavy chain variable domain comprising or consisting of SEQ ID NO: 82. The antibody may comprise the light chain of XBB-9, and not the heavy chain of XBB-9. For example, the antibody may comprise a CDRL1, CDRL2 and CDRL3 having the amino acid sequences specified in SEQ ID NOs: 88, 89 and 90, respectively. The antibody may comprise a light chain variable domain comprising or consisting of an amino acid sequence having ≥80%, ≥90%, ≥95%, ≥96%, ≥97%, ≥98%, ≥99% or 100% sequence identity to the light chain variable domain of antibody XBB-9 (i.e. SEQ ID NO: 84). The antibody may comprise a light chain variable domain comprising or consisting of SEQ ID NO: 84. The antibody in Table 1 may be XBB-1. Hence, an antibody of the invention may comprise the six CDRs of antibody XBB-1, which are CDRH1, CDRH2, CDRH3, CDRL1, CDRL2 and CDRL3 having the amino acid sequences specified in SEQ ID NOs: 5, 6, 7, 8, 9 and 10, respectively. The antibody of the invention may comprise a heavy chain variable domain comprising or consisting of an amino acid sequence having ≥80%, ≥90%, ≥95%, ≥96%, ≥97%, ≥98%, ≥99% or 100% sequence identity to the heavy chain variable domain of antibody XBB-1 (i.e. SEQ ID NO: 2). The antibody of the invention may comprise a light chain variable domain comprising or consisting of an amino acid sequence having ≥80%, ≥90%, ≥95%, ≥96%, ≥97%, ≥98%, ≥99% or 100% sequence identity to the light chain variable domain of antibody XBB-1 (i.e. SEQ ID NO: 4. The antibody of the invention may comprise a heavy chain variable domain and a light chain variable domain comprising or consisting of an amino acid sequence having ≥80%, ≥90%, ≥95%, ≥96%, ≥97%, ≥98%, ≥99% or 100% sequence identity to the heavy chain variable domain and light chain variable domain, respectively, of antibody XBB-1 (i.e. SEQ ID NOs: 2 and 4, respectively). The antibody of the invention may be a full-length antibody, for example, the antibody may comprise a heavy chain variable domain and a light chain variable domain as set out in SEQ ID NOs: 2 and 4, respectively, and a constant region, such as an IgA, IgD, IgE, IgG (IgG1, IgG2, IgG3 or IgG4) or IgM constant region. The antibody in Table 1 may be XBB-2. Hence, an antibody of the invention may comprise the six CDRs of antibody XBB-2, which are CDRH1, CDRH2, CDRH3, CDRL1, CDRL2 and CDRL3 having the amino acid sequences specified in SEQ ID NOs: 15, 16, 17, 18, 19 and 20, respectively. The antibody of the invention may comprise a heavy chain variable domain comprising or consisting of an amino acid sequence having ≥80%, ≥90%, ≥95%, ≥96%, ≥97%, ≥98%, ≥99% or 100% sequence identity to the heavy chain variable domain of antibody XBB-2 (i.e. SEQ ID NO: 12). The antibody of the invention may comprise a light chain variable domain comprising or consisting of an amino acid sequence having ≥80%, ≥90%, ≥95%, ≥96%, ≥97%, ≥98%, ≥99% or 100% sequence identity to the light chain variable domain of antibody XBB-2 (i.e. SEQ ID NO: 14. The antibody of the invention may comprise a heavy chain variable domain and a light chain variable domain comprising or consisting of an amino acid sequence having ≥80%, ≥90%, ≥95%, ≥96%, ≥97%, ≥98%, ≥99% or 100% sequence identity to the heavy chain variable domain and light chain variable domain, respectively, of antibody XBB-2 (i.e. SEQ ID NOs: 12 and 14, respectively). The antibody of the invention may be a full-length antibody, for example, the antibody may comprise a heavy chain variable domain and a light chain variable domain as set out in SEQ ID NOs: 12 and 14, respectively, and a constant region, such as an IgA, IgD, IgE, IgG (IgG1, IgG2, IgG3 or IgG4) or IgM constant region. The heavy chain domain of XBB-2 is derived from a IGHV3-53 v-region, and the inventors have previously demonstrated that switching of the heavy chains and light chains between antibodies derived from the same v-region (e.g. XBB-8 or XBB-9) and/or IGHV3-66 (e.g. XBB-3 or XBB-10) results in an antibody that is particularly useful with the invention (explained further below). Hence, an antibody of the invention may comprise the heavy chain of XBB-2, and not the light chain of XBB-2. For example, the antibody may comprise a CDRH1, CDRH2 and CDRH3 having the amino acid sequences specified in SEQ ID NOs: 15, 16 and 17, respectively. The antibody may comprise a heavy chain variable domain comprising or consisting of an amino acid sequence having ≥80%, ≥90%, ≥95%, ≥96%, ≥97%, ≥98%, ≥99% or 100% sequence identity to the heavy chain variable domain of antibody XBB-2 (i.e. SEQ ID NO: 12). The antibody may comprise a heavy chain variable domain comprising or consisting of SEQ ID NO: 12. The antibody may comprise the light chain of XBB-2, and not the heavy chain of XBB-2. For example, the antibody may comprise a CDRL1, CDRL2 and CDRL3 having the amino acid sequences specified in SEQ ID NOs: 18, 19 and 20, respectively. The antibody may comprise a light chain variable domain comprising or consisting of an amino acid sequence having ≥80%, ≥90%, ≥95%, ≥96%, ≥97%, ≥98%, ≥99% or 100% sequence identity to the light chain variable domain of antibody XBB-2 (i.e. SEQ ID NO: 14). The antibody may comprise a light chain variable domain comprising or consisting of SEQ ID NO: 14. The antibody in Table 1 may be XBB-3. Hence, an antibody of the invention may comprise the six CDRs of antibody XBB-3, which are CDRH1, CDRH2, CDRH3, CDRL1, CDRL2 and CDRL3 having the amino acid sequences specified in SEQ ID NOs: 25, 26, 27, 28, 29 and 30, respectively. The antibody of the invention may comprise a heavy chain variable domain comprising or consisting of an amino acid sequence having ≥80%, ≥90%, ≥95%, ≥96%, ≥97%, ≥98%, ≥99% or 100% sequence identity to the heavy chain variable domain of antibody XBB-3 (i.e. SEQ ID NO: 22). The antibody of the invention may comprise a light chain variable domain comprising or consisting of an amino acid sequence having ≥80%, ≥90%, ≥95%, ≥96%, ≥97%, ≥98%, ≥99% or 100% sequence identity to the light chain variable domain of antibody XBB-3 (i.e. SEQ ID NO: 24. The antibody of the invention may comprise a heavy chain variable domain and a light chain variable domain comprising or consisting of an amino acid sequence having ≥80%, ≥90%, ≥95%, ≥96%, ≥97%, ≥98%, ≥99% or 100% sequence identity to the heavy chain variable domain and light chain variable domain, respectively, of antibody XBB-3 (i.e. SEQ ID NOs: 22 and 24, respectively). The antibody of the invention may be a full-length antibody, for example, the antibody may comprise a heavy chain variable domain and a light chain variable domain as set out in SEQ ID NOs: 22 and 24, respectively, and a constant region, such as an IgA, IgD, IgE, IgG (IgG1, IgG2, IgG3 or IgG4) or IgM constant region. The heavy chain domain of XBB-3 is derived from a IGHV3-66 v-region, and the inventors have previously demonstrated that switching of the heavy chains and light chains between antibodies derived from the same v-region (e.g. XBB-10) and/or IGHV3-53 (e.g. XBB-2, XBB-8 or XBB-9) results in an antibody that is particularly useful with the invention (explained further below). Hence, an antibody of the invention may comprise the heavy chain of XBB-3, and not the light chain of XBB-3. For example, the antibody may comprise a CDRH1, CDRH2 and CDRH3 having the amino acid sequences specified in SEQ ID NOs: 25, 26 and 27, respectively. The antibody may comprise a heavy chain variable domain comprising or consisting of an amino acid sequence having ≥80%, ≥90%, ≥95%, ≥96%, ≥97%, ≥98%, ≥99% or 100% sequence identity to the heavy chain variable domain of antibody XBB-3 (i.e. SEQ ID NO: 22). The antibody may comprise a heavy chain variable domain comprising or consisting of SEQ ID NO: 22. The antibody may comprise the light chain of XBB-3, and not the heavy chain of XBB-3. For example, the antibody may comprise a CDRL1, CDRL2 and CDRL3 having the amino acid sequences specified in SEQ ID NOs: 28, 29 and 30, respectively. The antibody may comprise a light chain variable domain comprising or consisting of an amino acid sequence having ≥80%, ≥90%, ≥95%, ≥96%, ≥97%, ≥98%, ≥99% or 100% sequence identity to the light chain variable domain of antibody XBB-3 (i.e. SEQ ID NO: 24). The antibody may comprise a light chain variable domain comprising or consisting of SEQ ID NO: 24. The antibody in Table 1 may be XBB-4. Hence, an antibody of the invention may comprise the six CDRs of antibody XBB-4, which are CDRH1, CDRH2, CDRH3, CDRL1, CDRL2 and CDRL3 having the amino acid sequences specified in SEQ ID NOs: 35, 36, 37, 38, 39 and 40, respectively. The antibody of the invention may comprise a heavy chain variable domain comprising or consisting of an amino acid sequence having ≥80%, ≥90%, ≥95%, ≥96%, ≥97%, ≥98%, ≥99% or 100% sequence identity to the heavy chain variable domain of antibody XBB-4 (i.e. SEQ ID NO: 32). The antibody of the invention may comprise a light chain variable domain comprising or consisting of an amino acid sequence having ≥80%, ≥90%, ≥95%, ≥96%, ≥97%, ≥98%, ≥99% or 100% sequence identity to the light chain variable domain of antibody XBB-4 (i.e. SEQ ID NO: 34. The antibody of the invention may comprise a heavy chain variable domain and a light chain variable domain comprising or consisting of an amino acid sequence having ≥80%, ≥90%, ≥95%, ≥96%, ≥97%, ≥98%, ≥99% or 100% sequence identity to the heavy chain variable domain and light chain variable domain, respectively, of antibody XBB-4 (i.e. SEQ ID NOs: 32 and 34, respectively). The antibody of the invention may be a full-length antibody, for example, the antibody may comprise a heavy chain variable domain and a light chain variable domain as set out in SEQ ID NOs: 32 and 34, respectively, and a constant region, such as an IgA, IgD, IgE, IgG (IgG1, IgG2, IgG3 or IgG4) or IgM constant region. The antibody in Table 1 may be XBB-5. Hence, an antibody of the invention may comprise the six CDRs of antibody XBB-5, which are CDRH1, CDRH2, CDRH3, CDRL1, CDRL2 and CDRL3 having the amino acid sequences specified in SEQ ID NOs: 45, 46, 47, 48, 49 and 50, respectively. The antibody of the invention may comprise a heavy chain variable domain comprising or consisting of an amino acid sequence having ≥80%, ≥90%, ≥95%, ≥96%, ≥97%, ≥98%, ≥99% or 100% sequence identity to the heavy chain variable domain of antibody XBB-5 (i.e. SEQ ID NO: 42). The antibody of the invention may comprise a light chain variable domain comprising or consisting of an amino acid sequence having ≥80%, ≥90%, ≥95%, ≥96%, ≥97%, ≥98%, ≥99% or 100% sequence identity to the light chain variable domain of antibody XBB-5 (i.e. SEQ ID NO: 44. The antibody of the invention may comprise a heavy chain variable domain and a light chain variable domain comprising or consisting of an amino acid sequence having ≥80%, ≥90%, ≥95%, ≥96%, ≥97%, ≥98%, ≥99% or 100% sequence identity to the heavy chain variable domain and light chain variable domain, respectively, of antibody XBB-5 (i.e. SEQ ID NOs: 42 and 44, respectively). The antibody of the invention may be a full-length antibody, for example, the antibody may comprise a heavy chain variable domain and a light chain variable domain as set out in SEQ ID NOs: 42 and 44, respectively, and a constant region, such as an IgA, IgD, IgE, IgG (IgG1, IgG2, IgG3 or IgG4) or IgM constant region. The antibody in Table 1 may be XBB-6. Hence, an antibody of the invention may comprise the six CDRs of antibody XBB-6, which are CDRH1, CDRH2, CDRH3, CDRL1, CDRL2 and CDRL3 having the amino acid sequences specified in SEQ ID NOs: 55, 56, 57, 58, 59 and 60, respectively. The antibody of the invention may comprise a heavy chain variable domain comprising or consisting of an amino acid sequence having ≥80%, ≥90%, ≥95%, ≥96%, ≥97%, ≥98%, ≥99% or 100% sequence identity to the heavy chain variable domain of antibody XBB-6 (i.e. SEQ ID NO: 52). The antibody of the invention may comprise a light chain variable domain comprising or consisting of an amino acid sequence having ≥80%, ≥90%, ≥95%, ≥96%, ≥97%, ≥98%, ≥99% or 100% sequence identity to the light chain variable domain of antibody XBB-6 (i.e. SEQ ID NO: 54. The antibody of the invention may comprise a heavy chain variable domain and a light chain variable domain comprising or consisting of an amino acid sequence having ≥80%, ≥90%, ≥95%, ≥96%, ≥97%, ≥98%, ≥99% or 100% sequence identity to the heavy chain variable domain and light chain variable domain, respectively, of antibody XBB-6 (i.e. SEQ ID NOs: 52 and 54, respectively). The antibody of the invention may be a full-length antibody, for example, the antibody may comprise a heavy chain variable domain and a light chain variable domain as set out in SEQ ID NOs: 52 and 54, respectively, and a constant region, such as an IgA, IgD, IgE, IgG (IgG1, IgG2, IgG3 or IgG4) or IgM constant region. The antibody in Table 1 may be XBB-7. Hence, an antibody of the invention may comprise the six CDRs of antibody XBB-7, which are CDRH1, CDRH2, CDRH3, CDRL1, CDRL2 and CDRL3 having the amino acid sequences specified in SEQ ID NOs: 65, 66, 67, 68, 69 and 70, respectively. The antibody of the invention may comprise a heavy chain variable domain comprising or consisting of an amino acid sequence having ≥80%, ≥90%, ≥95%, ≥96%, ≥97%, ≥98%, ≥99% or 100% sequence identity to the heavy chain variable domain of antibody XBB-7 (i.e. SEQ ID NO: 62). The antibody of the invention may comprise a light chain variable domain comprising or consisting of an amino acid sequence having ≥80%, ≥90%, ≥95%, ≥96%, ≥97%, ≥98%, ≥99% or 100% sequence identity to the light chain variable domain of antibody XBB-7 (i.e. SEQ ID NO: 64. The antibody of the invention may comprise a heavy chain variable domain and a light chain variable domain comprising or consisting of an amino acid sequence having ≥80%, ≥90%, ≥95%, ≥96%, ≥97%, ≥98%, ≥99% or 100% sequence identity to the heavy chain variable domain and light chain variable domain, respectively, of antibody XBB-7 (i.e. SEQ ID NOs: 62 and 64, respectively). The antibody of the invention may be a full-length antibody, for example, the antibody may comprise a heavy chain variable domain and a light chain variable domain as set out in SEQ ID NOs: 62 and 64, respectively, and a constant region, such as an IgA, IgD, IgE, IgG (IgG1, IgG2, IgG3 or IgG4) or IgM constant region. The antibody in Table 1 may be XBB-8. Hence, an antibody of the invention may comprise the six CDRs of antibody XBB-8, which are CDRH1, CDRH2, CDRH3, CDRL1, CDRL2 and CDRL3 having the amino acid sequences specified in SEQ ID NOs: 75, 76, 77, 78, 79 and 80, respectively. The antibody of the invention may comprise a heavy chain variable domain comprising or consisting of an amino acid sequence having ≥80%, ≥90%, ≥95%, ≥96%, ≥97%, ≥98%, ≥99% or 100% sequence identity to the heavy chain variable domain of antibody XBB-8 (i.e. SEQ ID NO: 72). The antibody of the invention may comprise a light chain variable domain comprising or consisting of an amino acid sequence having ≥80%, ≥90%, ≥95%, ≥96%, ≥97%, ≥98%, ≥99% or 100% sequence identity to the light chain variable domain of antibody XBB-8 (i.e. SEQ ID NO: 74. The antibody of the invention may comprise a heavy chain variable domain and a light chain variable domain comprising or consisting of an amino acid sequence having ≥80%, ≥90%, ≥95%, ≥96%, ≥97%, ≥98%, ≥99% or 100% sequence identity to the heavy chain variable domain and light chain variable domain, respectively, of antibody XBB-8 (i.e. SEQ ID NOs: 72 and 74, respectively). The antibody of the invention may be a full-length antibody, for example, the antibody may comprise a heavy chain variable domain and a light chain variable domain as set out in SEQ ID NOs: 72 and 74, respectively, and a constant region, such as an IgA, IgD, IgE, IgG (IgG1, IgG2, IgG3 or IgG4) or IgM constant region. The heavy chain domain of XBB-8 is derived from a IGHV3-53 v-region, and the inventors have previously demonstrated that switching of the heavy chains and light chains between antibodies derived from the same v-region (e.g. XBB-2 or XBB-9) and/or IGHV3-66 (e.g. XBB-3 or XBB-10) results in an antibody that is particularly useful with the invention (explained further below). Hence, an antibody of the invention may comprise the heavy chain of XBB-8, and not the light chain of XBB-8. For example, the antibody may comprise a CDRH1, CDRH2 and CDRH3 having the amino acid sequences specified in SEQ ID NOs: 75, 76 and 77, respectively. The antibody may comprise a heavy chain variable domain comprising or consisting of an amino acid sequence having ≥80%, ≥90%, ≥95%, ≥96%, ≥97%, ≥98%, ≥99% or 100% sequence identity to the heavy chain variable domain of antibody XBB-8 (i.e. SEQ ID NO: 72). The antibody may comprise a heavy chain variable domain comprising or consisting of SEQ ID NO: 82. The antibody may comprise the light chain of XBB-8, and not the heavy chain of XBB-8. For example, the antibody may comprise a CDRL1, CDRL2 and CDRL3 having the amino acid sequences specified in SEQ ID NOs: 78, 79 and 80, respectively. The antibody may comprise a light chain variable domain comprising or consisting of an amino acid sequence having ≥80%, ≥90%, ≥95%, ≥96%, ≥97%, ≥98%, ≥99% or 100% sequence identity to the light chain variable domain of antibody XBB-8 (i.e. SEQ ID NO: 74). The antibody may comprise a light chain variable domain comprising or consisting of SEQ ID NO: 74. The antibody in Table 1 may be XBB-10. Hence, an antibody of the invention may comprise the six CDRs of antibody XBB-10, which are CDRH1, CDRH2, CDRH3, CDRL1, CDRL2 and CDRL3 having the amino acid sequences specified in SEQ ID NOs: 95, 96, 97, 98, 99 and 100, respectively. The antibody of the invention may comprise a heavy chain variable domain comprising or consisting of an amino acid sequence having ≥80%, ≥90%, ≥95%, ≥96%, ≥97%, ≥98%, ≥99% or 100% sequence identity to the heavy chain variable domain of antibody XBB-10 (i.e. SEQ ID NO: 92). The antibody of the invention may comprise a light chain variable domain comprising or consisting of an amino acid sequence having ≥80%, ≥90%, ≥95%, ≥96%, ≥97%, ≥98%, ≥99% or 100% sequence identity to the light chain variable domain of antibody XBB-10 (i.e. SEQ ID NO: 94. The antibody of the invention may comprise a heavy chain variable domain and a light chain variable domain comprising or consisting of an amino acid sequence having ≥80%, ≥90%, ≥95%, ≥96%, ≥97%, ≥98%, ≥99% or 100% sequence identity to the heavy chain variable domain and light chain variable domain, respectively, of antibody XBB-10 (i.e. SEQ ID NOs: 92 and 94, respectively). The antibody of the invention may be a full-length antibody, for example, the antibody may comprise a heavy chain variable domain and a light chain variable domain as set out in SEQ ID NOs: 92 and 94, respectively, and a constant region, such as an IgA, IgD, IgE, IgG (IgG1, IgG2, IgG3 or IgG4) or IgM constant region. The heavy chain domain of XBB-10 is derived from a IGHV3-66 v-region, and the inventors have previously demonstrated that switching of the heavy chains and light chains between antibodies derived from the same v-region (e.g. XBB-3) and/or IGHV3-53 (e.g. XBB-2, XBB-2 or XBB-9) results in an antibody that is particularly useful with the invention (explained further below). Hence, an antibody of the invention may comprise the heavy chain of XBB-10, and not the light chain of XBB-10. For example, the antibody may comprise a CDRH1, CDRH2 and CDRH3 having the amino acid sequences specified in SEQ ID NOs: 95, 96 and 97, respectively. The antibody may comprise a heavy chain variable domain comprising or consisting of an amino acid sequence having ≥80%, ≥90%, ≥95%, ≥96%, ≥97%, ≥98%, ≥99% or 100% sequence identity to the heavy chain variable domain of antibody XBB-10 (i.e. SEQ ID NO: 92). The antibody may comprise a heavy chain variable domain comprising or consisting of SEQ ID NO: 92. The antibody may comprise the light chain of XBB-10, and not the heavy chain of XBB-10. For example, the antibody may comprise a CDRL1, CDRL2 and CDRL3 having the amino acid sequences specified in SEQ ID NOs: 98, 99 and 100, respectively. The antibody may comprise a light chain variable domain comprising or consisting of an amino acid sequence having ≥80%, ≥90%, ≥95%, ≥96%, ≥97%, ≥98%, ≥99% or 100% sequence identity to the light chain variable domain of antibody XBB-10 (i.e. SEQ ID NO: 94). The antibody may comprise a light chain variable domain comprising or consisting of SEQ ID NO: 94. The neutralisation data presented herein were performed in vitro and may underestimate in vivo neutralization due to antibody dependent cell mediated cytotoxicity and complement activity. Mixed chain antibodies of the invention An antibody of the invention may comprise a light chain variable domain comprising CDRL1, CDRL2 and CDRL3 from a first antibody in Table 1 and a heavy chain variable domain comprising CDRH1, CDRH2 and CDRH3 from a second antibody in Table 1, with the proviso that the first and second antibodies are different. Such antibodies are referred to as mixed chain antibodies herein. The first and second antibodies from Table 1 may be derived from the same germline heavy chain or light chain v-region. The heavy chain v-region may be IGHV3-53 and/or IGHV3-66. The light chain v-region may be IGκV1-33, IGκV1-39, or IGλV2-14. Examples of the mixed chain antibodies useful with the invention are provided in Tables 2 to 4. Table 2 shows examples of mixed chain antibodies generated from antibodies in Table 1 that are derived from the same germline heavy chain IGHV 3-53. Table 3 shows examples of mixed chain antibodies generated from antibodies in Table 1 that are derived from the same germline heavy chain IGHV 3-66. Table 4 shows examples of mixed chain antibodies generated from antibodies in Table 1 that are derived from the germline heavy chain IGHV 3-53 and IGHV 3-66. Hence, an antibody of the invention may comprise a heavy chain variable domain comprising CDRH1, CDRH2 and CDRH3 from a first antibody in Table 1 and a light chain variable domain comprising CDRL1, CDRL2 and CDRL3 from a second antibody in Table 1, with the proviso that the first and second antibodies are different. The antibody may comprise a heavy chain variable domain amino acid sequence having at least 80% sequence identity to the heavy chain variable domain from a first antibody in Table 1, and a light chain variable domain amino acid sequence having at least 80% sequence identity to the light chain variable domain from a second antibody in Table 1, with the proviso that the first and second antibodies are different. For example, the antibody may comprise a heavy chain variable domain comprising or consisting of an amino acid sequence having ≥80%, ≥90%, ≥95%, ≥96%, ≥97%, ≥98%, ≥99% or 100% sequence identity to the heavy chain variable domain of an antibody in Table 1, and a light chain variable domain comprising or consisting of an amino acid sequence having ≥80%, ≥90%, ≥95%, ≥96%, ≥97%, ≥98%, ≥99% or 100% sequence identity to the light chain variable domain of an antibody in Table 1, with the proviso that the first and second antibodies are different. An antibody of the invention may comprise a heavy chain variable domain comprising CDRH1, CDRH2 and CDRH3 from a first antibody in Table 1 and a light chain variable domain comprising CDRL1, CDRL2 and CDRL3 from a second antibody in Table 1, and comprise a heavy chain variable domain comprising or consisting of an amino acid sequence having ≥80%, ≥90%, ≥95%, ≥96%, ≥97%, ≥98%, ≥99% or 100% sequence identity to the heavy chain variable domain of the first antibody in Table 1, and a light chain variable domain comprising or consisting of an amino acid sequence having ≥80%, ≥90%, ≥95%, ≥96%, ≥97%, ≥98%, ≥99% or 100% sequence identity to the light chain variable domain of the second antibody in Table 1, with the proviso that the first and second antibodies are different. The first antibody and the second antibody may both be selected from the group consisting of XBB-2, XBB-8 and XBB-9. The heavy chain variable domain of each these antibodies are derived from IGHV 3-53. The resulting mixed chain antibodies are set out in Table 2, i.e. XBB-8H/XBB-2L, XBB-9H/XBB-2L, XBB-2H/XBB-8L, XBB-9H/XBB- 8L, XBB-2H/XBB-9L, or XBB-8H/XBB-9L. Hence, the antibody of the invention may comprise all six CDRs (CDRH1-3 and CDRL1-3) of any one of the mixed chain antibody as set out in Table 2, i.e. XBB-8H/XBB-2L, XBB-9H/XBB-2L, XBB-2H/XBB-8L, XBB- 9H/XBB-8L, XBB-2H/XBB-9L, and XBB-8H/XBB-9L. The antibody of the invention may comprise a heavy chain variable domain and a light chain variable domain comprising or consisting of an amino acid sequence having at least 80% (e.g. ≥80%, ≥90%, ≥95%, ≥96%, ≥97%, ≥98%, ≥99% or 100%) sequence identity to the corresponding variable domain of any one any of the mixed chain antibody as set out in Table 2, i.e. XBB- 8H/XBB-2L, XBB-9H/XBB-2L, XBB-2H/XBB-8L, XBB-9H/XBB-8L, XBB-2H/XBB- 9L, and XBB-8H/XBB-9L. The first antibody and the second antibody may both be selected from the group consisting of XBB-3and XBB-10. The heavy chain variable domain of each these antibodies are derived from IGHV 3-66. The resulting mixed chain antibodies are set out in Table 3, i.e. XBB-10H/XBB-3L and XBB-3H/XBB-10L. Hence, the antibody of the invention may comprise all six CDRs (CDRH1-3 and CDRL1-3) of any one of the mixed chain antibody as set out in Table 3, i.e. XBB-10H/XBB-3L and XBB-3H/XBB-10L. The antibody of the invention may comprise a heavy chain variable domain and a light chain variable domain comprising or consisting of an amino acid sequence having at least 80% (e.g. ≥80%, ≥90%, ≥95%, ≥96%, ≥97%, ≥98%, ≥99% or 100%) sequence identity to the corresponding variable domain of any one any of the mixed chain antibody as set out in Table 3, i.e. XBB-10H/XBB-3L and XBB-3H/XBB-10L. The first antibody and the second antibody may both be selected from the group consisting of XBB-2, XBB-3, XBB-8, XBB-9 and XBB-10. The heavy chain variable domain of each these antibodies are derived from IGHV 3-53 and/or IGHV 3-66. The resulting mixed chain antibodies are set out in Table 4, i.e. XBB-8H/XBB-2L, XBB- 9H/XBB-2L, XBB-3H/XBB-2L, XBB-10H/XBB-2L, XBB-2H/XBB-8L, XBB-9H/XBB- 8L, XBB-3H/XBB-8L, XBB-10H/XBB-8L, XBB-2H/XBB-9L, XBB-8H/XBB-9L, XBB- 3H/XBB-9L, XBB-10H/XBB-9L, XBB-2H/XBB-3L, XBB-8H/XBB-3L, XBB-9H/XBB- 3L, XBB-10H/XBB-3L, XBB-2H/XBB-10L, XBB-8H/XBB-10L, XBB-9H/XBB-10L, and XBB-3H/XBB-10L. Hence, the antibody of the invention may comprise all six CDRs (CDRH1-3 and CDRL1-3) of any one of the mixed chain antibody as set out in Table 4, i.e. XBB-8H/XBB-2L, XBB-9H/XBB-2L, XBB-3H/XBB-2L, XBB-10H/XBB-2L, XBB- 2H/XBB-8L, XBB-9H/XBB-8L, XBB-3H/XBB-8L, XBB-10H/XBB-8L, XBB-2H/XBB- 9L, XBB-8H/XBB-9L, XBB-3H/XBB-9L, XBB-10H/XBB-9L, XBB-2H/XBB-3L, XBB- 8H/XBB-3L, XBB-9H/XBB-3L, XBB-10H/XBB-3L, XBB-2H/XBB-10L, XBB-8H/XBB- 10L, XBB-9H/XBB-10L, and XBB-3H/XBB-10L. The antibody of the invention may comprise a heavy chain variable domain and a light chain variable domain comprising or consisting of an amino acid sequence having at least 80% (e.g. ≥80%, ≥90%, ≥95%, ≥96%, ≥97%, ≥98%, ≥99% or 100%) sequence identity to the corresponding variable domain of any one any of the mixed chain antibody as set out in Table 4, i.e. XBB-8H/XBB-2L, XBB-9H/XBB-2L, XBB-3H/XBB-2L, XBB-10H/XBB-2L, XBB-2H/XBB-8L, XBB- 9H/XBB-8L, XBB-3H/XBB-8L, XBB-10H/XBB-8L, XBB-2H/XBB-9L, XBB-8H/XBB- 9L, XBB-3H/XBB-9L, XBB-10H/XBB-9L, XBB-2H/XBB-3L, XBB-8H/XBB-3L, XBB- 9H/XBB-3L, XBB-10H/XBB-3L, XBB-2H/XBB-10L, XBB-8H/XBB-10L, XBB- 9H/XBB-10L, and XBB-3H/XBB-10L. Properties of the antibodies of the invention An antibody of the invention may be or may comprise a modification from the amino acid sequence of an antibody in Tables 1 to 4, whilst maintaining the activity and/or function of the antibody. The modification may a substitution, deletion and/or addition. For example, the modification may comprise 1, 2, 3, 4, 5, up to 10, up to 20, up to 30 or more amino acid substitutions and/or deletions from the amino acid sequence of an antibody in Tables 1 to 4. For example, the modification may comprise an amino acid substituted with an alternative amino acid having similar properties. Some properties of the 20 main amino acids, which can be used to select suitable substituents, are as follows: Ala aliphatic, hydrophobic, neutral Met hydrophobic, neutral Cys polar, hydrophobic, neutral Asn polar, hydrophilic, neutral Asp polar, hydrophilic, charged (-) Pro hydrophobic, neutral Glu polar, hydrophilic, charged (-) Gln polar, hydrophilic, neutral Phe aromatic, hydrophobic, neutral Arg polar, hydrophilic, charged (+) Gly aliphatic, neutral Ser polar, hydrophilic, neutral His aromatic, polar, hydrophilic, Thr polar, hydrophilic, neutral charged (+) Ile aliphatic, hydrophobic, neutral Val aliphatic, hydrophobic, neutral Lys polar, hydrophilic, charged (+) Trp aromatic, hydrophobic, neutral Leu aliphatic, hydrophobic, neutral Tyr aromatic, polar, hydrophobic The modification may comprise a derivatised amino acid, e.g. a labelled or non- natural amino acid, providing the function of the antibody is not significantly adversely affected. Modification of antibodies of the invention as described above may be prepared during synthesis of the antibody or by post-production modification, or when the antibody is in recombinant form using the known techniques of site-directed mutagenesis, random mutagenesis, or enzymatic cleavage and/or ligation of nucleic acids. Antibodies of the invention may be modified (e.g. as described above) to improve the potency of said antibodies or to adapt said antibodies to new SARS-CoV-2 variants. The modifications may be amino acid substitutions to adapt the antibody to substitutions in a virus variant. For example, the known mode of binding of an antibody to the spike protein (e.g. by crystal structure determination, or modelling) may be used to identify the amino acids of the antibody that interact with the substitution in the virus variant. This information can then be used to identify possible substitutions of the antibody that will compensate for the change in the epitope characteristics. For example, a substitution of a hydrophobic amino acid in the spike protein to a negatively changes amino acid may be compensated by substituting the amino acid from the antibody that interacts with said amino acid in the spike protein to a positively charged amino acid. Methods for identifying residues of an antibody that may be substituted are encompassed by the present disclosure, for example, by determining the structure of antibody-antigen complexes as described herein. The antibodies of the invention may contain one or more modifications to increase their cross-lineage neutralisation property. For example, E484 of the spike protein, which is a key residue that mediates the interaction with ACE2, is mutated in almost all currently circulating SARS-CoV-2 strains (see e.g. Figure 1A, demonstrating that all strain shown comprise E484 mutation, e.g. an E484K or E484A mutation) resulting in differing neutralisation effects of the antibodies. Thus, antibodies that bind to E484 can be modified to compensate for the changes in E484 of the spike protein. For example, when E484 is mutated from a negatively charged amino acid (Glu) to a positively charged amino acid (Arg), the amino acid residues of antibodies that bind to or near E484 may be mutated to compensate for the change in charge. Antibodies of the invention may be isolated antibodies. A composition consisting of an isolated antibody is substantially free of other antibodies having different antigenic specificities. The term 'antibody' as used herein may relate to whole antibodies (i.e. comprising the elements of two heavy chains and two light chains inter-connected by disulphide bonds) as well as antigen-binding fragments thereof. Antibodies typically comprise immunologically active portions of immunoglobulin (Ig) molecules, i.e., molecules that contain an antigen binding site that specifically binds (immunoreacts with) an antigen. By "specifically binds" or "immunoreacts with", it is meant that the antibody reacts with one or more antigenic determinants of the desired antigen and does not react with other polypeptides. Each heavy chain is comprised of a heavy chain variable region (abbreviated herein as HCVR or VH) and at least one heavy chain constant region. Each light chain is comprised of a light chain variable region (abbreviated herein as LCVR or VL) and a light chain constant region. The variable regions of the heavy and light chains contain a binding domain that interacts with an antigen. The VH and VL regions can be further subdivided into regions of hypervariability, termed complementarity determining regions (CDR), interspersed with regions that are more conserved, termed framework regions (FR). Antibodies may include, but are not limited to, polyclonal, monoclonal, chimeric, dAb (domain antibody), single chain, Fab, Fab’ and F(ab’)2 fragments, scFvs, and Fab expression libraries An antibody of the invention may be a monoclonal antibody. Monoclonal antibodies (mAbs) of the invention may be produced by a variety of techniques, including conventional monoclonal antibody methodology, for example those disclosed in “Monoclonal Antibodies: a manual of techniques” (Zola H, 1987, CRC Press) and in “Monoclonal Hybridoma Antibodies: techniques and applications” (Hurrell JGR, 1982 CRC Press). An antibody of the invention may be multispecific, such as bispecific. A bispecific antibody of the invention binds two different epitopes. The epitopes may be in the same protein (e.g. two epitopes in spike protein of SARS-CoV-2) or different proteins (e.g. one epitope in spike protein and one epitope in another protein (such as coat protein) of SARS- CoV-2). A bispecific antibody of the invention may bind to two separate epitopes on the spike protein of SARS-CoV-2. The bispecific antibody may bind to the NTD of the spike protein and to the RBD of the spike protein. The bispecific antibody may bind to two different epitopes in the RBD of the spike protein. One or more (e.g. two) antibodies of the invention can be coupled to form a multispecific (e.g. bispecific) antibody. Methods to prepare multispecific, e.g. bispecific, antibodies are well known in the art. An antibody may be selected from the group consisting of single chain antibodies, single chain variable fragments (scFvs), variable fragments (Fvs), fragment antigen- binding regions (Fabs), recombinant antibodies, monoclonal antibodies, fusion proteins comprising the antigen-binding domain of a native antibody or an aptamer, single-domain antibodies (sdAbs), also known as VHH antibodies, nanobodies (Camelid-derived single- domain antibodies), shark IgNAR-derived single-domain antibody fragments called VNAR, diabodies, triabodies, Anticalins, aptamers (DNA or RNA) and active components or fragments thereof. The constant region domains of an antibody molecule of the invention, if present, may be selected having regard to the proposed function of the antibody molecule, and in particular the effector functions which may be required. For example, the constant region domains may be human IgA, IgD, IgE, IgG or IgM domains. Typically, the constant regions are of human origin. In particular, human IgG (i.e. IgG1, IgG2, IgG3 or IgG4) constant region domains may be used. Typically, the constant region is a human IgG1 constant region. The light chain constant region may be either lambda or kappa. Antibodies of the invention may be mono-specific or multi-specific (e.g. bi- specific). A multi-specific antibody comprises at least two different variable domains, wherein each variable domain is capable of binding to a separate antigen or to a different epitope on the same antigen. An antibody of the invention may be a chimeric antibody, a CDR-grafted antibody, a nanobody, a human or humanised antibody. Typically, the antibody is a human antibody. Fully human antibodies are those antibodies in which the variable regions and the constant regions (where present) of both the heavy and the light chains are all of human origin, or substantially identical to sequences of human origin, but not necessarily from the same antibody. The antibody of the invention may be a full-length antibody. For example, the antibody may comprise a heavy chain variable domain of an antibody in Tables 1 to 4, a light chain variable domain of an antibody in Tables 1 to 4, and a constant region, such as an IgA, IgD, IgE, IgG (IgG1, IgG2, IgG3 or IgG4) or IgM constant region. For example, the antibody of the invention may be a full length XBB-9 antibody, i.e. comprising the heavy chain variable domain of XBB-9 (SEQ ID NO: 82) and the light chain variable domain of XBB-9 (SEQ ID NO: 84), and a constant region (e.g. comprising an IgG1 constant region). The antibody of the invention may be an antigen-binding fragment. An antigen- binding fragment of the invention binds to the same epitope of the parent antibody, i.e. the antibody from which the antigen-binding fragment is derived. An antigen-binding fragment of the invention typically retains the parts of the parent antibody that interact with the epitope. The antigen-binding fragment typically comprise the complementarity- determining regions (CDRs) that interact with the antigen, such as one, two, three, four, five or six CDRs. The antigen-binding fragment may further comprise the structural scaffold surrounding the CDRs of the parent antibody, such as the variable region domains of the heavy and/or light chains. Typically, the antigen-binding fragment retains the same or similar binding affinity to the antigen as the parent antibody. An antigen-binding fragment does not necessarily have an identical sequence to the parent antibody. The antigen-binding fragment may have ≥70%, ≥80%, ≥90%, ≥95%, ≥96%, ≥97%, ≥98%, ≥99% or 100% sequence identity with the respective CDRs of the parent antibody. The antigen-binding fragment may have ≥70%, ≥80%, ≥90%, ≥95%, ≥96%, ≥97%, ≥98%, ≥99% or 100% sequence identity with the respective variable region domains of the parent antibody. Typically, the non-identical amino acids of a variable region are not in the CDRs. The antigen-binding fragments of antibodies of the invention retain the ability to selectively bind to an antigen. Antigen-binding fragments of antibodies include single chain antibodies (i.e. a full-length heavy chain and light chain); Fab, modified Fab, Fab', modified Fab', F(ab')2, Fv, Fab-Fv, Fab-dsFv, single domain antibodies (e.g. VH or VL or VHH), scFv. An antigen-binding function of an antibody can be performed by fragments of a full-length antibody. The methods for creating and manufacturing these antibody fragments are well known in the art (see for example Verma R et al., 1998, J. Immunol. Methods, 216, 165-181). Methods for screening antibodies of the invention that do not share 100% amino acid sequence identity with one of the antibodies disclosed herein, that possess the desired specificity, affinity and functional activity include the methods described herein, e.g. enzyme linked immunosorbent assays, biacore, focus reduction neutralisation assay (FRNT), and other techniques known within the art. With regards to function, an antibody of the invention may be able to neutralise at least one biological activity of SAR-CoV-2 (a neutralising antibody), particularly to neutralise virus infectivity. Neutralisation may also be determined using IC₅₀ or IC₉₀ values. For example, the antibody may have an IC₅₀ value of ≤0.1µg/ml, ≤0.05µg/ml, ≤0.01µg/ml ≤0.005µg/ml or ≤0.002µg/ml. In some instances an antibody of the invention may have an IC₅₀ value of between 0.0001 µg/ml and 0.1 µg/ml, sometimes between 0.0001µg/ml and 0.05 µg/ml or even between 0.0001 µg/ml and 0.001 µg/ml. For example, the IC₅₀ values of some of the antibodies of Table 1 are provided in Table 5 and Figure 4. The ability of an antibody to neutralise virus infectivity may be measured using an appropriate assay, particularly using a cell-based neutralisation assay, as is known in the art. For example, the neutralisation ability may be measured in a focus reduction neutralisation assay (FRNT) where the reduction in the number of cells (e.g. human cells) infected with the virus (e.g. for 2 hours at 37 ºC) in the presence of the antibody is compared to a negative control in which no antibodies were added. An antibody of the invention may block the interaction between the spike protein of SAR-CoV-2 with the cell surface receptor, angiotensin-converting enzyme 2 (ACE2), of the target cell, e.g. by direct blocking or by disrupting the pre-fusion conformation of the spike protein. Blocking of the interaction between spike and ACE2 can be total or partial. For example, an antibody of the invention may reduce spike-ACE2 formation by ≥50%, ≥60%, ≥70%, ≥80%, ≥90%, ≥95%, ≥99% or 100%. Blocking of spike-ACE2 formation can be measured by any suitable means known in the art, for example, by ELISA. Most antibodies showing neutralisation also showed blocking of the interaction between the spike protein and ACE2. Furthermore, a number of non-neutralising antibodies are good ACE2 blockers. In terms of binding kinetics, an antibody of the invention may have an affinity constant (KD) value for the spike protein of SARS-CoV-2 of ≤5nM, ≤4nM, ≤3nM, ≤2nM, ≤1nM, ≤0.5nM, ≤0.4nM, ≤0.3nM, ≤0.2nM or ≤0.1nM. The KD value can be measured by any suitable means known in the art, for example, by ELISA or Surface Plasmon Resonance (Biacore) at 25 °C. Binding affinity (K_D) may be quantified by determining the dissociation constant (K_d) and association constant (K_a) for an antibody and its target. For example, the antibody may have an association constant (K_a) of ≥ 10000 M^-1s^-1, ≥ 50000 M^-1s^-1, ≥ 100000 M^-1s^-1, ≥ 200000 M^-1s^-1 or ≥ 500000 M^-1s^-1, and/or a dissociation constant (K_d) of ≤ 0.001 s^-1, ≤ 0.0005 s^-1, ≤ 0.004 s^-1, ≤ 0.003 s^-1, ≤ 0.002 s^-1 or ≤ 0.0001 s^-1. An antibody of the invention is preferably able to provide in vivo protection in coronavirus (e.g. SARS-CoV-2) infected animals. For example, administration of an antibody of the invention to coronavirus (e.g. SARS-CoV-2) infected animals may result in a survival rate of ≥30%, ≥40%, ≥50%, ≥60%, ≥70%, ≥80%, ≥90%, ≥95% or 100%. Survival rates may be determined using routine methods. An antibody of the invention may have any combination of one or more of the above properties. An antibody of the invention may bind to the same epitope as, or compete for binding to SARS-CoV-2 spike protein with, any one of the antibodies described herein (i.e. in particular with antibodies with the heavy and light chain variable regions described above). Methods for identifying antibodies binding to the same epitope, or cross- competing with one another, are known in the art and described herein. Fc regions An antibody of the invention may or may not comprise an Fc domain. The antibodies of the invention may be modified in the Fc region in order to improve their stability. Such modifications are known in the art. Modifications may improve the stability of the antibody during storage of the antibody. The in vivo half-life of the antibody may be improved by modifications of the Fc-region. For example, cysteine residue(s) can be introduced into the Fc region, thereby allowing interchain disulphide bond formation in this region. The homodimeric antibody thus generated can have improved internalization capability and/or increased complement- mediated cell killing and antibody-dependent cellular cytotoxicity (ADCC). (See Caron et al., J. Exp Med., 176: 1191-1195 (1992) and Shopes, J. Immunol., 148: 2918-2922 (1992)). Alternatively, an antibody can be engineered that has dual Fc regions and can thereby have enhanced complement lysis and ADCC capabilities. (See Stevenson et al., Anti-Cancer Drug Design, 3: 219-230 (1989)). For example, an antibody of the invention may be modified to promote the interaction of the Fc domain with FcRn. The Fc domain may be modified to improve the stability of the antibody by affecting Fc and FcRn interaction at low pH, such as in the endosome. The M252Y/S254T/T256E (YTE) mutation may be used to improve the half- life of an IgG1 antibody. The antibody may be modified to affect the interaction of the antibody with other receptors, such as FcγRI, FcγRIIA, FcγRIIB, FcγRIII, and FcαR. Such modifications may be used to affect the effector functions of the antibody. An antibody of the invention may comprise an altered Fc domain as described herein below. An antibody of the invention may comprise an Fc domain, but the sequence of the Fc domain has been altered to modify one or more Fc effector functions. An antibody of the invention may comprise a “silenced” Fc region. For example, an antibody of the invention may not display the effector function or functions associated with a normal Fc region. An Fc region of an antibody of the invention does not bind to one or more Fc receptors. An antibody of the invention may not comprise a CH₂ domain. An antibody of the invention may not comprise a CH₃ domain. An antibody of the invention may comprise additional CH₂ and/or CH₃ domains. An antibody of the invention may not bind Fc receptors. An antibody of the invention may not bind complement. An antibody of the invention may not bind FcγR, but does bind complement. An antibody of the invention in general may comprise modifications that alter serum half-life of the antibody. Hence, An antibody of the invention may have Fc region modification(s) that alter the half-life of the antibody. Such modifications may be present as well as those that alter Fc functions. An antibody of the invention may have modification(s) that alter the serum half-life of the antibody. An antibody of the invention may comprise a human constant region, for instance IgA, IgD, IgE, IgG or IgM domains. In particular, human IgG constant region domains may be used, especially of the IgG1 and IgG3 isotypes when the antibody molecule is intended for therapeutic uses where antibody effector functions are required. Typically, the constant region is a human IgG1 constant region. Alternatively, IgG2 and IgG4 isotypes may be used when the antibody molecule is intended for therapeutic purposes and antibody effector functions are not required. The antibody heavy chain may comprise a CH₁ domain and the antibody light chain comprises a CL domain, either kappa or lambda. The antibody heavy chain may comprise a CH₁ domain, a CH₂ domain and a CH₃ domain and the antibody light chain comprises a CL domain, either kappa or lambda. The four human IgG isotypes bind the activating Fcγ receptors (FcγRI, FcγRIIa, Fc ^RIIc, FcγRIIIa), the inhibitory FcγRIIb receptor, and the first component of complement (C1q) with different affinities, yielding very different effector functions (Bruhns P. et al., 2009. Specificity and affinity of human Fcγ receptors and their polymorphic variants for human IgG subclasses. Blood.113(16):3716-25), see also Jeffrey B. Stavenhagen, et al. Cancer Research 2007 Sep 15; 67(18):8882-90. An antibody of the invention may not bind to Fc receptors. The antibody may bind to one or more type of Fc receptors. In the Fc region employed herein may be mutated, in particular a mutation described herein. The Fc mutation is selected from the group comprising a mutation to remove or enhance binding of the Fc region to an Fc receptor, a mutation to increase or remove an effector function, a mutation to increase or decrease half-life of the antibody and a combination of the same. Where reference is made to the impact of a modification it may be demonstrated by comparison to the equivalent antibody but lacking the modification. Some antibodies that selectively bind FcRn at pH 6.0, but not pH 7.4, exhibit a higher half-life in a variety of animal models. Several mutations located at the interface between the CH₂ and CH₃ domains, such as T250Q/M428L (Hinton PR. et al., 2004. Engineered human IgG antibodies with longer serum half-lives in primates. J Biol Chem. 279(8):6213-6) and M252Y/S254T/T256E + H433K/N434F (Vaccaro C. et al., 2005. Engineering the Fc region of immunoglobulin G to modulate in vivo antibody levels. Nat Biotechnol.23(10):1283-8), have been shown to increase the binding affinity to FcRn and the half-life of IgG1 in vivo. Hence, modifications may be present at M252/S254/T256 + H44/N434 that alter serum half-life and in particular M252Y/S254T/T256E + H433K/N434F may be present. It may be desired to increase half-life. It may be actually desired to decrease serum half-life of the antibody and so modifications may be present that decrease serum half-life. Numerous mutations have been made in the CH₂ domain of human IgG1 and their effect on ADCC and CDC tested in vitro (Idusogie EE. et al., 2001. Engineered antibodies with increased activity to recruit complement. J Immunol.166(4):2571-5). Notably, alanine substitution at position 333 was reported to increase both ADCC and CDC. Hence, a modification at position 333 may be present, and in particular one that alters ability to recruit complement. Lazar et al. described a triple mutant (S239D/I332E/A330L) with a higher affinity for FcγRIIIa and a lower affinity for FcγRIIb resulting in enhanced ADCC (Lazar GA. et al., 2006). Hence, modifications at S239/I332/A330 may be present, particularly those that alter affinity for Fc receptors and in particular S239D/I332E/A330L. Engineered antibody Fc variants with enhanced effector function. PNAS 103(11): 4005– 4010). The same mutations were used to generate an antibody with increased ADCC (Ryan MC. et al., 2007. Antibody targeting of B-cell maturation antigen on malignant plasma cells. Mol. Cancer Ther., 6: 3009 – 3018). Richards et al. studied a slightly different triple mutant (S239D/I332E/G236A) with improved FcγRIIIa affinity and FcγRIIa/FcγRIIb ratio that mediates enhanced phagocytosis of target cells by macrophages (Richards JO et al 2008. Optimization of antibody binding to Fcgamma RIIa enhances macrophage phagocytosis of tumor cells. Mol Cancer Ther.7(8):2517-27). For example, S239D/I332E/G236A modifications may be therefore present. An antibody of the invention may have a modified hinge region and/or CH1 region. Alternatively, the isotype employed may be chosen as it has a particular hinge regions. Epitope comprising residues 455 and 456 The inventors identified that SARS-CoV-2 may be under immune selective pressure to acquire mutations in a region in the spike protein that contains amino acid residues at positions 455 and 456 (numbering relative to the spike protein of the hCoV- 19/Wuhan/WIV04/2019 strain). This was evident from the blocking or severely impairment of activity of 7 out of 10 potent XBB mAb when residues 455 and 456 were mutated, e.g. in XBB.1.5.10, AG.1.5 (F456L) and XBB.1.5.70 (L455F and F456L) (see Figure Table 5 and Figure 4). Therefore, antibodies that target this particular epitope would result in a resilient antibody. Hence, the invention provides a method of generating an antibody capable of binding to the spike protein of SARS-CoV-2, comprising raising an antibody against an epitope comprising amino acid residues at positions 455 and 456 in the spike protein of coronavirus SARS-CoV-2, relative to the spike protein of the hCoV- 19/Wuhan/WIV04/2019 strain. The method may comprise screening for antibodies capable of binding to an epitope comprising amino acid residues at positions 455 and 456, one or both of which may be substituted, e.g. with specific substitutions, such as L455F and/or F456L, or with random substitutions. The method may comprise screening for antibodies that bind to the same epitope as antibody XBB-9. The method may comprise carrying out competition studies with antibody XBB-9. The competition studies may be carried out by any means known to the skilled person, for example, the biolayer interferometry studies. The invention also provides an antibody obtained by this method. Similarly, the invention provides an antibody obtainable by this method. The invention also provides an antibody capable of binding to an epitope comprising amino acid residues at positions 455 and 456 in the spike protein of coronavirus SARS-CoV-2, relative to the spike protein of the hCoV- 19/Wuhan/WIV04/2019 strain. The invention also provides an antibody capable of binding to the same epitope on the spike protein as antibody XBB-9. The invention also provides an antibody that competes with antibody XBB-9 for binding to the spike protein. The antibody may not be Omi-42, which is disclosed in Nutalai et al., Cell, 2022, 185(12):2116-2131.e18; GB 2202232.1 and GB 2203423.5). The antibody may not be BA.4/5-1 or BA.4/5-2, which are disclosed in Stuart et al., 21 March 2023, Research Square pre-print; https://doi.org/10.21203/rs.3.rs-2684849/v1, and GB2304512.3. The skilled person is readily able to determine the binding site (epitope) of an antibody using standard techniques, such as those described in the Examples of the application. The skilled person could also readily determine whether an antibody binds to the same epitope as, or competes for binding with, an antibody described herein by using routine methods known in the art. For example, to determine if a test antibody (i.e. where it is not known whether the test antibody competes with other antibodies for binding to an antigen) binds to the same epitope as an antibody described herein (referred to a “reference antibody” in the following paragraphs), the reference antibody is allowed to bind to a protein or peptide under saturating conditions. Next, the ability of a test antibody to bind to the protein or peptide is assessed. If the test antibody is able to bind to the protein or peptide following saturation binding with the reference antibody, it can be concluded that the test antibody binds to a different epitope than the reference antibody. On the other hand, if the test antibody is not able to bind to protein or peptide following saturation binding with the reference antibody, then the test antibody may bind to the same epitope as the epitope bound by the reference antibody of the invention. To determine if an antibody competes for binding with a reference antibody, the above-described binding methodology is performed in two orientations. In a first orientation, the reference antibody is allowed to bind to a protein/peptide under saturating conditions followed by assessment of binding of the test antibody to the protein/peptide molecule. In a second orientation, the test antibody is allowed to bind to the protein/peptide under saturating conditions followed by assessment of binding of the reference antibody to the protein/peptide. If, in both orientations, only the first (saturating) antibody is capable of binding to the protein/peptide, then it is concluded that the test antibody and the reference antibody compete for binding to the protein/peptide. As will be appreciated by the skilled person, an antibody that competes for binding with a reference antibody may not necessarily bind to the identical epitope as the reference antibody, but may sterically block binding of the reference antibody by binding an overlapping or adjacent epitope. Two antibodies bind to the same or overlapping epitope if each competitively inhibits (blocks) binding of the other to the antigen. Alternatively, two antibodies have the same epitope if essentially all amino acid mutations in the antigen that reduce or eliminate binding of one antibody reduce or eliminate binding of the other. Two antibodies have overlapping epitopes if some amino acid mutations that reduce or eliminate binding of one antibody reduce or eliminate binding of the other. Additional routine experimentation (e.g., peptide mutation and binding analyses) can then be carried out to confirm whether the observed lack of binding of the test antibody is in fact due to binding to the same epitope as the reference antibody or if steric blocking (or another phenomenon) is responsible for the lack of observed binding. Experiments of this sort can be performed using ELISA, RIA, surface plasmon resonance, flow cytometry or any other quantitative or qualitative antibody-binding assay available in the art. Cross-competing antibodies can be identified using any suitable method in the art, for example by using competition ELISA or BIAcore assays where binding of the cross competing antibody to a particular epitope on the spike protein prevents the binding of an antibody of the invention or vice versa. The antibody may produce ≥50%, ≥60%, ≥70%, ≥80%, ≥90% or 100% reduction of binding of the specific antibody disclosed herein. Other techniques that may be used to determine antibody epitopes include hydrogen/deuterium exchange, X-ray crystallography and peptide display libraries (as described in the Examples). A combination of these techniques may be used to determine the epitope of the test antibody. The approaches used herein could be applied equally to other data, e.g. surface plasmon resonance or ELISA, and provides a general way of rapidly determining locations from highly redundant competition experiments. The numbering of the spike protein, such as the modified spike protein, provided herein is in relation to the numbering of the hCoV-19/Wuhan/WIV04/2019 (WIV04) strain, also provided herein as SEQ ID NO: 103, unless otherwise stated. The spike protein used herein may be derived from any variant of SARS-CoV-2. The reference to SEQ ID NO: 103 is to provide a numbering system for identification of amino acid positions in variants wherein the absolute numbering differs. It is within the means of the skilled person to align amino acid sequences of spike proteins from different variants to determine the corresponding position of an amino acid in a variant, when compared to SEQ ID NO: 103, using sequence alignment tools. Major public V regions Public V-regions, also described as public V-genes herein, are the V regions of the germline heavy chain and light chain regions that are found in a large proportion of the antibody responses to SARS-CoV-2 found within the population. The inventors found that many individuals utilise the same v-regions from their germline v-region repertoire when generating antibodies to elicit an immune response against SARS-CoV-2 variants, in particular BA.2.86 as explained further below. As used herein, an antibody “derived” from a specific v-region refers to antibodies that were generated by V(D)J recombination using that germline v-region sequence. For example, the germline IGHV3-53 v-region sequence may undergo somatic recombination and somatic mutation to arrive at an antibody that specifically binds to the spike protein of SARS-CoV-2. The nucleotide sequence encoding the antibody does not comprise a sequence identical to the IGHV3-53 germline sequence, nevertheless, the antibody is still derived from this v-region. An antibody of the invention typically comprises no more than 20 non-silent mutations in the v-region, when compared to the germline sequence, such as no more than 17 non-silent mutations. An antibody of the invention typically comprises between 5-20 non-silent mutations in the v-region, when compared to the germline sequence, such as between 6-18, 7-17 and 8-15 non-silent mutations. An antibody of the invention typically comprises between 5-15 amino acid changes in the v-region, when compared to the amino acid sequence encoded by the germline sequence, such as between 6-14 and 7-12 amino acid changes. Germline v-region sequences are well known in the art, and methods of identifying whether a certain region of an antibody is derived from a particular germline v-region sequence are also well known in the art. For example, the germline v-region sequences of IGHV3-53 and IGκV1-33 are set out in SEQ ID NOs: 101 and 102, respectively. An antibody of the invention may derive from a v-region selected from IGHV3-53, IGHV3-66, IGHV1-69, IGHV3-15, IGHV3-72, IGHV3-9, or IGHV3-7. The inventors found that the potent neutralising antibodies identified herein comprised non-silent mutations in the CDRs of these v-regions, as set out in Table 9. Thus, an antibody of the invention may be encoded by a v-region selected from IGHV3-53, IGHV3-66, IGHV1-69, IGHV3-15, IGHV3-72, IGHV3-9, or IGHV3-7, and having 5-20 non-silent nucleotide mutations, such as 6-18, 7-17 or 8-15 non-silent mutations, when compared to the naturally occurring germline sequence. An antibody of the invention may be encoded by a v-region selected from IGHV3-53 and/or IGHV3-66, and having 5-20 non-silent nucleotide mutations, such as 6-18, 7-17 or 8-15 non-silent mutations, when compared to the naturally occurring germline sequence. A silent mutation is defined herein is a change in the nucleotide sequence without a change in the amino acid sequence for which the nucleotide sequence encodes. A non- silent mutation is therefore a mutation that leads to a change in the amino acid sequence encoded by the nucleotide sequence. The inventors have surprisingly found that the light chain variable region of two antibodies having the same heavy chain v-region may be exchanged to produce a mixed- chain antibody comprising the heavy chain variable region of a first antibody and the light chain variable region of a second antibody. For example, the two antibodies may both comprise a heavy chain variable region derived from IGHV3-53. Preferably, both antibodies also comprise a light chain variable region derived from the same light chain v- region, although this is not essential because, for example, the light chain of some antibodies having a heavy chain variable region derived from IGHV3-53 may be matched with any heavy chain variable region derived from IGHV3-53 and lead to a potent neutralising antibody. As described above, the two antibodies may comprise a heavy chain variable region derived from IGHV3-53 and/or IGHV3-66. An antibody of the invention may comprise the CDRs of a heavy chain variable domain of an antibody derived from a major public v-region selected from IGHV3-53 and/or IGHV3-66, such as antibodies XBB-2, XBB-8 and XBB-9 for IGHV3-53, and XBB-3and XBB-10 for IGHV3-66. The SEQ ID NOs corresponding to the CDRs of each of these antibodies are shown in Table 1. The invention also provides a method of generating an antibody that binds specifically to the spike protein of SARS-CoV-2 (e.g. a SARS-CoV-2 strain of the Victoria, Alpha, Beta, Gamma, Delta, BA.1, BA.1.1, BA.2, BA.10.4, BA.2.12.1, BA.2.30.2, BA.2.75, BA.2.75.2, BA.4/5, BA.4.6, BQ.1, BQ.1.1, BJ.1, BS.1, BF.7, BN.1, XBB, XBB.1, XBB.1.5, BA.2, XBB.1.5.10, XBB.1.5.70 and BA.2.86), the method comprising identifying two or more antibodies derived from the same light chain and/or heavy chain v-regions, replacing the light chain of a first antibody with the light chain of a second antibody, to thereby generate a mixed-chain antibody comprising the heavy chain of the first antibody and the light chain of the second antibody. The method may further comprise determining the affinity for and/or neutralisation of SARS-CoV-2 of the mixed- chain antibody. The method may further comprise comparing the affinity of the mixed- chain antibody with that of the first and/or second antibodies. The method may further comprise selecting a mixed chain antibody that has the same or greater affinity than the first and/or second antibodies. The invention also provides an antibody that specifically binds to the BA.2.86 variant of SARS-CoV-2, wherein the antibody has a v-region derived from IGHV3-53 and/or IGHV3-66. It has been surprisingly discovered that antibody responses to infection with the BA.2.86 variant of SARS-CoV-2 is biased towards antibodies with heavy chain variable regions derived from IGHV3-53 and IGHV3-66. Where the antibody heavy chain is derived from IGHV3-53, the antibody of the invention may comprise the CDRH1, CDRH2 and CDRH3 from XBB-2, XBB-8 and XBB-9. Where the antibody heavy chain is derived from IGHV3-66, the antibody of the invention may comprise the CDRH1, CDRH2 and CDRH3 from XBB-3and XBB-10. Antibody conjugates The invention also pertains to immunoconjugates comprising an antibody conjugated to a cytotoxic agent such as a toxin (e.g., an enzymatically active toxin of bacterial, fungal, plant, or animal origin, or fragments thereof), or a radioactive isotope (i.e., a radioconjugate). Conjugates of the antibody and cytotoxic agent may be made using a variety of bifunctional protein-coupling agents known in the art. An antibody, of the invention may be conjugated to a molecule that modulates or alters serum half-life. An antibody, of the invention may bind to albumin, for example in order to modulate the serum half-life. An antibody of the invention may also include a binding region specific for albumin. An antibody of the invention may include a peptide linker which is an albumin binding peptide. Examples of albumin binding peptides are included in WO2015/197772 and WO2007/106120 the entirety of which are incorporated by reference. Polynucleotides, vectors and host cells The invention also provides one or more isolated polynucleotides (e.g. DNA) encoding the antibody of the invention. The polynucleotide sequence may be collectively present on more than one polynucleotide, but collectively together they are able to encode an antibody of the invention. For example, the polynucleotides may encode the heavy and/or light chain variable regions(s) of an antibody of the invention. The polynucleotides may encode the full heavy and/or light chain of an antibody of the invention. Typically, one polynucleotide would encode each of the heavy and light chains. Hence, the invention provides a first polynucleotide encoding the heavy chain variable domain of an antibody of the invention and a second polynucleotide encoding the light chain variable domain of said antibody. The invention also provides a polynucleotide encoding the heavy chain variable domain and the light chain variable domain of an antibody according to the invention. Polynucleotides which encode an antibody of the invention can be obtained by methods well known to those skilled in the art. For example, DNA sequences coding for part or all of the antibody heavy and light chains may be synthesised as desired from the corresponding amino acid sequences. General methods by which the vectors may be constructed, transfection methods and culture methods are well known to those skilled in the art. In this respect, reference is made to “Current Protocols in Molecular Biology”, 1999, F. M. Ausubel (ed), Wiley Interscience, New York and the Maniatis Manual produced by Cold Spring Harbor Publishing. A polynucleotide of the invention may be provided in the form of an expression cassette, which includes control sequences operably linked to the inserted sequence, thus allowing for expression of the antibody of the invention in vivo. Hence, the invention also provides one or more expression cassettes encoding the one or more polynucleotides that encoding an antibody of the invention. These expression cassettes, in turn, are typically provided within vectors (e.g. plasmids or recombinant viral vectors). Hence, the invention provides a vector encoding an antibody of the invention. The invention also provides vectors which collectively encode an antibody of the invention. The vectors may be cloning vectors or expression vectors. A suitable vector may be any vector which is capable of carrying a sufficient amount of genetic information, and allowing expression of a polypeptide of the invention. The polynucleotides, expression cassettes or vectors of the invention are introduced into a host cell, e.g. by transfection. Hence, the invention also provides a host cell comprising the one or more polynucleotides, expression cassettes or vectors of the invention. The polynucleotides, expression cassettes or vectors of the invention may be introduced transiently or permanently into the host cell, allowing expression of an antibody from the one or more polynucleotides, expression cassettes or vectors. Such host cells include transient, or preferably stable higher eukaryotic cell lines, such as mammalian cells or insect cells, lower eukaryotic cells, such as yeast, or prokaryotic cells, such as bacteria cells. Particular examples of cells include mammalian HEK293, such as HEK293F, HEK293T, HEK293S or HEK Expi293F, CHO, HeLa, NS0 and COS cells, or any other cell line used herein, such as the ones used in the Examples. Preferably the cell line selected will be one which is not only stable, but also allows for mature glycosylation. The invention also provides a process for the production of an antibody of the invention, comprising culturing a host cell containing one or more vectors of the invention under conditions suitable for the expression of the antibody from the one or more polynucleotides of the invention, and isolating the antibody from said culture. Combination of antibodies Certain Table 1 antibodies may be particularly effective when used in combination, e.g. to minimise loss of activity due to SARS-CoV-2 variants, maximise therapeutic effects and/or increase diagnostic power. Useful combinations include antibodies that do not cross-compete with one another and/or bind to non-overlapping epitopes. Thus, the invention provides a combination of the antibodies of the invention, wherein each antibody is capable of binding to the spike protein of coronavirus SARS- CoV-2, wherein at least one antibody comprises all six CDRs of an antibody in Table 1. The invention also provides a combination of antibodies, comprising a first antibody which is an antibody according to the invention, in combination with at least one further antibody that does not compete with the first antibody for binding to the spike protein of coronavirus SARS-CoV-2. The first and the at least one further antibodies may bind to different epitopes in the same domain, or may bind to epitopes in different domains in the spike protein. For example, the first antibody may bind to the RBD domain and the at least one further antibody may bind to the NTD of the spike protein. Alternatively, the first antibody may bind to the NTD domain and the at least one further antibody may bind to the RBD of the spike protein. A combination of the antibodies of the invention may be useful as a therapeutic cocktail. Hence, the invention also provides a pharmaceutical composition comprising a combination of the antibodies of the invention. This is because a new SARS-CoV-2 variant may circulate that is not neutralised by a first of the antibodies in the cocktail but is neutralised by a second antibody in the cocktail, whilst the converse may be true for a further SARS-CoV-2 variant that circulates. Thus, a cocktail of antibodies of the invention may provide a more robust treatment for SARS-CoV-2 than a single antibody of the invention alone. A combination of the antibodies of the invention may be useful for diagnosis. Hence, the invention also provides a diagnostic kit comprising a combination of the antibodies of the invention. Also provided herein are methods of diagnosing a disease or complication associated with coronavirus infections in a subject, as explained further below. A fully cross-neutralising antibody, e.g. XBB-9, may be used as a reference to confirm the presence and/or amount of any variants of concern (VoC) SARS-CoV-2 in the sample. An antibody that binds to a limited number of VoCs may be used to confirm the presence and/or amount of that VoC in the sample. For example, if XBB-9 exhibits binding to the sample but XBB-10 does not exhibit binding to the sample of SARS-CoV-2, then the spike protein may be the spike protein of the XBB.1.5.10 or XBB.1.5.70 VoC. This may be determined by any method known to the skilled person, such as via an immunoassay, e.g. an ELISA or an immunochromatographic assay. Reduced binding may be determined by comparison and/or normalisation to the reference, and/or by comparison to positive/negative control samples or data. Pharmaceutical composition The invention provides a pharmaceutical composition comprising an antibody of the invention. The composition may comprise a combination (such as two, three or four) of the antibodies of the invention. The pharmaceutical composition may also comprise a pharmaceutically acceptable carrier. The composition of the invention may include one or more pharmaceutically acceptable salts. A "pharmaceutically acceptable salt" refers to a salt that retains the desired biological activity of the parent compound and does not impart any undesired toxicological effects. Examples of such salts include acid addition salts and base addition salts. Suitable pharmaceutically acceptable carriers comprise aqueous carriers or diluents. Examples of suitable aqueous carriers include water, buffered water and saline. Other suitable pharmaceutically acceptable carriers include ethanol, polyols (such as glycerol, propylene glycol, polyethylene glycol, and the like), and suitable mixtures thereof, vegetable oils, such as olive oil, and injectable organic esters, such as ethyl oleate. In many cases, it will be desirable to include isotonic agents, for example, sugars, polyalcohols such as mannitol, sorbitol, or sodium chloride in the composition. Therapeutic compositions typically must be sterile and stable under the conditions of manufacture and storage. The composition can be formulated as a solution, microemulsion, liposome, or other ordered structure suitable to high drug concentration. Pharmaceutical compositions of the invention may comprise additional therapeutic agents, for example an anti-viral agent. The anti-viral agent may bind to coronavirus and inhibit viral activity. Alternatively, the anti-viral agent may not bind directly to coronavirus but still affect viral activity/infectivity. The anti-viral agent could be a further anti-coronavirus antibody, which binds somewhere on SARS-CoV-2 other than the spike protein. Examples of an anti-viral agent useful with the invention include Remdesivir, Lopinavir, ritonavir, APN01, Favilavir, Nirmatrelvir, and/or molnupiravir. The additional therapeutic agent may be an anti-inflammatory agent, such as a corticosteroid (e.g. Dexamethasone) or a non-steroidal anti-inflammatory drug (e.g. Tocilizumab). The additional therapeutic agent may be an anti-coronavirus vaccine. The pharmaceutical composition may be administered subcutaneously, intravenously, intradermally, intramuscularly, intranasally or orally. Also within the scope of the invention are kits comprising antibodies or other compositions of the invention and instructions for use. The kit may further contain one or more additional reagents, such as an additional therapeutic or prophylactic agent as discussed herein. Methods and uses of the invention The invention further relates to the use of the antibodies and the pharmaceutical compositions, described herein, e.g. in a method for treatment of the human or animal body by therapy, or in a diagnostic method. The method of treatment may be therapeutic or prophylactic. For example, the invention relates to methods of treating coronavirus (e.g. SARS- CoV-2) infections, a disease or complication associated therewith, e.g. COVID-19. The method may comprise administering a therapeutically effective amount of an antibody, a combination of antibodies, or a pharmaceutical composition of the invention. The method may further comprise identifying the presence of coronavirus, or fragments thereof, in a sample, e.g. SARS-CoV-2, from the subject. The invention also relates to an antibody, a combination of antibodies, or a pharmaceutical composition according to the invention for use in a method of treating coronavirus (e.g. SARS-CoV-2) infections, a disease or complication associated therewith, e.g. COVID-19. The invention also relates to a method of formulating a composition for treating coronavirus (e.g. SARS-CoV-2) infections, a disease or complication associated therewith, e.g. COVID-19, wherein said method comprises mixing an antibody, a combination of antibodies, or a pharmaceutical composition according to the invention with an acceptable carrier to prepare said composition. The invention also relates to the use of an antibody, a combination of antibodies, or a pharmaceutical composition according to the invention for treating coronavirus (e.g. SARS-CoV-2) infections or a disease or complication associated therewith, e.g. COVID- 19. The invention also relates to the use of an antibody, a combination of antibodies, or a pharmaceutical composition according to the invention for the manufacture of a medicament for treating or preventing coronavirus (e.g. SARS-CoV-2) infections or a disease or complication associated therewith, e.g. COVID-19. The invention also relates to preventing, treating or diagnosing coronavirus infection caused by any SARS-CoV-2 strain. The coronavirus infection may be caused by any SARS-CoV-2 strain. The SARS-CoV-2 strain may be the earliest identified Wuhan strain (hCoV- 19/Wuhan/WIV04/2019 (WIV04); GISAID accession no. EPI_ISL_402124), and variants thereof. For example, the SARS-CoV-2 strain may be a member of lineage Victoria, Alpha, Beta, Gamma, Delta, BA.1, BA.1.1, BA.2, BA.2.10.4, BA.2.12.1, BA.2.3.20, BA.2.75, BA.2.75.2, BA.4/5, BA.4.6, BQ.1, BQ.1.1, BJ.1, BS.1, BF.7, BN.1, XBB, XBB.1, XBB1.5, XBB.1.5.10, XBB.1.5.70, or BA.2.86. The SARS-CoV-2 strain may be a member of lineage BA.2, BA.4/5, XBB.1.5, XBB.1.5.10, XBB.1.5.70, BA.2.86 or BQ.1.1. The SARS-CoV-2 strain may be a member of lineage BA.2.86. The strain may be an as-yet-unidentified strain of SARS-CoV-2 comprising mutations in the spike protein already identified in the existing strains, as shown in Figure 1. The SARS-CoV-2 strain may comprise one or more mutations, e.g. in the spike protein, relative to the hCoV-19/Wuhan/WIV04/2019 (WIV04) (GISAID accession no. EPI_ISL_402124). In other words, the SARS-CoV-2 strain may be a modified hCoV- 19/Wuhan/WIV04/2019 (WIV04) strain comprising one or more modifications, e.g. in the spike protein. The mutation may be the mutations (e.g. substitutions) observed in the BA.2.86 strain of SARS-CoV-2, e.g. as set out in Figure 1A. The mutation may be the mutations (e.g. substitutions) observed in the Victoria, Alpha, Beta, Gamma, Delta, BA.1, BA.1.1, BA.2, BA.2.10.4, BA.2.12.1, BA.2.3.20, BA.2.75, BA.2.75.2, BA.4/5, BA.4.6, BQ.1, BQ.1.1, BJ.1, BS.1, BF.7, BN.1, XBB, XBB.1, XBB1.5, XBB.1.5.10, XBB.1.5.70, or BA.2.86 strains of SARS-CoV-2. The mutations of some SARS-CoV-2 strains are provided in Figure 1A. All of the antibodies provided in Table 1 are effective in neutralising the BA.2.86 SARS-Cov-2 strain (see Figure 4 and Table 5). Hence, the invention may relate to these antibodies for use in treating, prevent, treating or diagnosing coronavirus infection caused by a SARS-Cov-2 strain. The methods and uses of the invention may comprise inhibiting the disease state (such as COVID-19), e.g. arresting its development; and/or relieving the disease state (such as COVID-19), e.g. causing regression of the disease state until a desired endpoint is reached. The methods and uses of the invention may comprise the amelioration or the reduction of the severity, duration or frequency of a symptom of the disease state (such as COVID-19) (e.g. lessen the pain or discomfort), and such amelioration may or may not be directly affecting the disease. The symptoms or complications may be fever, headache, fatigue, loss of appetite, myalgia, diarrhoea, vomiting, abdominal pain, dehydration, respiratory tract infections, cytokine storm, acute respiratory distress syndrome (ARDS) sepsis, and/or organ failure (e.g. heart, kidneys, liver, GI, lungs). The methods and uses of the invention may lead to a decrease in the viral load of coronavirus (e.g. SARS-CoV-2), e.g. by ≥10%, ≥20%, ≥30%, ≥40%, ≥50%, ≥60%, ≥70%, ≥80%, ≥90%, or 100% compared to pre-treatment. Methods of determining viral load are well known in the art, e.g. infection assays. The methods and uses of the invention may comprise preventing the coronavirus infection from occurring in a subject (e.g. humans), in particular, when such subject is predisposed to complications associated with coronavirus infection. The invention also relates to identifying subjects that have a coronavirus infection, such as by SARS-CoV-2. For example, the methods and uses of the invention may involve identifying the presence of coronavirus (e.g. SARS-CoV-2), or a protein or a fragment thereof, in a sample. The detection may be carried out in vitro or in vivo. The invention may relate to population screening. The invention relates to identifying any SARS-CoV-2 strain, as described herein. The invention may also relate to a method of identifying escape mutants of SARS- CoV-2, comprising contacting a sample with a combination of antibodies of the invention and identifying if each antibody binds to the virus. The term “escape mutants” refers to variants of SARS-CoV-2 comprising non-silent mutations that may affect the efficacy of existing treatments of SARS-CoV-2 infection. Typically, the non-silent mutations are on an epitope recognised by a prior art antibody and/or antibodies described herein that specifically binds to an epitope of SARS-CoV-2, e.g. on the spike protein of SARS-CoV-2. If the antibody does not bind to the target, it may indicate that the target comprises a mutation that may alter the efficacy of existing SARS-CoV-2 treatments. The methods and uses of the invention may include contacting a sample with an antibody or a combination of the antibodies of the invention, and detecting the presence or absence of an antibody-antigen complex, wherein the presence of the antibody-antigen complex indicates that the subject is infected with SARS-CoV-2. Methods of determining the presence of an antibody-antigen complex are known in the art. For example, in vitro detection techniques include enzyme linked immunosorbent assays (ELISAs), Western blots, immunoprecipitations, and immunofluorescence. In vivo techniques include introducing into a subject a labelled anti-analyte protein antibody. For example, the antibody can be labelled with a radioactive marker whose presence and location in a subject can be detected by standard imaging techniques. The detection techniques may provide a qualitative or a quantitative readout depending on the assay employed. Typically, the invention relates to methods and uses for a human subject in need thereof. However, non-human animals such as rats, rabbits, sheep, pigs, cows, cats, or dogs is also contemplated. The subject may be at risk of exposure to coronavirus infection, such as a healthcare worker or a person who has come into contact with an infected individual. A subject may have visited or be planning to visit a country known or suspected of having a coronavirus outbreak. A subject may also be at greater risk, such as an immunocompromised individual, for example an individual receiving immunosuppressive therapy or an individual suffering from human immunodeficiency syndrome (HIV) or acquired immune deficiency syndrome (AIDS). The subject may be asymptomatic or pre-symptomatic. The subject may be early, middle or late phase of the disease. The subject may be in hospital or in the community at first presentation, and/or later times in hospital. The subject may be male or female. The subject is typically male. The subject may not have been infected with coronavirus, such as SARS-CoV-2. The subject may have a predisposition to the more severe symptoms or complications associated with coronavirus infections. The method or use of the invention may comprise a step of identifying whether or not a patient is at risk of developing the more severe symptoms or complications associated with coronavirus. In embodiments of the invention relating to prevention or treatment, the subject may or may not have been diagnosed to be infected with coronavirus, such as SARS-CoV- 2. The invention relates to analysing samples from subjects. The sample may be tissues, cells and biological fluids isolated from a subject, as well as tissues, cells and fluids present within a subject. The sample may be blood and a fraction or component of blood including blood serum, blood plasma, or lymph. Typically, the sample is from a throat swab, nasal swab, or saliva. The antibody-antigen complex detection assays may be performed in situ, in which case the sample is a tissue section (fixed and/or frozen) of the tissue obtained from biopsies or resections from a subject. In the embodiments of the invention where the antibodies pharmaceutical compositions and combinations are administered, they may be administered subcutaneously, intravenously, intradermally, orally, intranasally, intramuscularly or intracranially. Typically, the antibodies pharmaceutical compositions and combinations are administered intravenously or subcutaneously. The dose of an antibody may vary depending on the age and size of a subject, as well as on the disease, conditions and route of administration. Antibodies may be administered at a dose of about 0.1 mg/kg body weight to a dose of about 100 mg/kg body weight, such as at a dose of about 5 mg/kg to about 10 mg/kg. Antibodies may also be administered at a dose of about 50 mg/kg, 10 mg/kg or about 5 mg/kg body weight. A combination of the invention may for example be administered at a dose of about 5 mg/kg to about 10 mg/kg for each antibody, or at a dose of about 10 mg/kg or about 5 mg/kg for each antibody. Alternatively, a combination may be administered at a dose of about 5 mg/kg total (e.g. a dose of 1.67 mg/kg of each antibody in a three antibody combination). The antibody or combination of antibodies of the invention may be administered in a multiple dosage regimen. For example, the initial dose may be followed by administration of a second or plurality of subsequent doses. The second and subsequent doses may be separated by an appropriate time. As discussed above, the antibodies of the invention are typically used in a single pharmaceutical composition/combination (co-formulated). However, the invention also generally includes the combined use of antibodies of the invention in separate preparations/compositions. The invention also includes combined use of the antibodies with additional therapeutic agents, as described above. Combined administration of the two or more agents and/or antibodies may be achieved in a number of different ways. All the components may be administered together in a single composition. Each component may be administered separately as part of a combined therapy. For example, the antibody of the invention may be administered before, after or concurrently with another antibody, or binding fragment thereof, of the invention. The particularly useful combinations are described above for example. For example, the antibody of the invention may be administered before, after or concurrently with an anti-viral agent or an anti-inflammatory agent. In embodiments where the invention relates to detecting the presence of coronavirus, e.g. SARS-CoV-2, or a protein or a fragment thereof, in a sample, the antibody contains a detectable label. Methods of attaching a label to an antibody are known in the art, e.g. by direct labelling of the antibody by coupling (i.e., physically linking) a detectable substance to the antibody. Alternatively, the antibody may be indirect labelled, e.g. by reactivity with another reagent that is directly labelled. Examples of indirect labelling include detection of a primary antibody using a fluorescently-labelled secondary antibody and end-labelling of a DNA probe with biotin such that it can be detected with fluorescently-labelled streptavidin. The detection may further comprise: (i) an agent known to be useful for detecting the presence of coronavirus, , e.g. SARS-CoV-2, or a protein or a fragment thereof, e.g. an antibody against other epitopes of the spike protein, or other proteins of the coronavirus, such as an anti-nucleocapsid antibody; and/or (ii) an agent known to not be capable of detecting the presence of coronavirus, , e.g. SARS-CoV-2, or a fragment thereof, i.e. providing a negative control. In certain embodiments, the antibody is modified to have increased stability. Suitable modifications are explained above. The invention also encompasses kits for detecting the presence of coronavirus, e.g. SARS-CoV-2, in a sample. For example, the kit may comprise: a labelled antibody or a combination of labelled antibodies of the invention; means for determining the amount of coronavirus, e.g. SARS-CoV-2, in a sample; and means for comparing the amount of coronavirus, e.g. SARS-CoV-2, in the sample with a standard. The labelled antibody or the combination of labelled antibodies can be packaged in a suitable container. The kit can further comprise instructions for using the kit to detect coronavirus, e.g. SARS-CoV-2, in a sample. The kit may further comprise other agents known to be useful for detecting the presence of coronavirus, as discussed above. For example, the antibodies or combinations of antibodies of the invention are used in a lateral flow test. Typically, the lateral flow test kit is a hand-held device with an absorbent pad, which based on a series of capillary beds, such as pieces of porous paper, microstructured polymer, or sintered polymer. The test runs the liquid sample along the surface of the pad with reactive molecules that show a visual positive or negative result. The test may further comprise using other agents known to be useful for detecting the presence of coronavirus, e.g. SARS-CoV-2, or a fragment thereof, as discussed above, such as anti- an anti-nucleocapsid antibody. Other It is to be understood that different applications of the disclosed antibodies combinations, or pharmaceutical compositions of the invention may be tailored to the specific needs in the art. It is also to be understood that the terminology used herein is for the purpose of describing particular embodiments of the invention only, and is not intended to be limiting. In addition as used in this specification and the appended claims, the singular forms “a”, “an”, and “the” include plural references unless the content clearly dictates otherwise. Thus, for example, reference to “an antibody” includes two or more “antibodies”. Furthermore, when referring to “≥x” herein, this means equal to or greater than x. When referred to “≤x” herein, this means less than or equal to x. For the purpose of this invention, in order to determine the percent identity of two sequences (such as two polynucleotide or two polypeptide sequences), the sequences are aligned for optimal comparison purposes (e.g. gaps can be introduced in a first sequence for optimal alignment with a second sequence). The nucleotide or amino acid residues at each position are then compared. When a position in the first sequence is occupied by the same nucleotide or amino acid as the corresponding position in the second sequence, then the nucleotides or amino acids are identical at that position. The percent identity between the two sequences is a function of the number of identical positions shared by the sequences (i.e., % identity = number of identical positions /total number of positions in the reference sequence × 100). Typically the sequence comparison is carried out over the length of the reference sequence. For example, if the user wished to determine whether a given (“test”) sequence is 95% identical to SEQ ID NO: 3, SEQ ID NO: 3 would be the reference sequence. To assess whether a sequence is at least 95% identical to SEQ ID NO: 3 (an example of a reference sequence), the skilled person would carry out an alignment over the length of SEQ ID NO: 3, and identify how many positions in the test sequence were identical to those of SEQ ID NO: 3. If at least 95% of the positions are identical, the test sequence is at least 95% identical to SEQ ID NO: 3. If the sequence is shorter than SEQ ID NO: 3, the gaps or missing positions should be considered to be non-identical positions. The skilled person is aware of different computer programs that are available to determine the homology or identity between two sequences. For instance, a comparison of sequences and determination of percent identity between two sequences can be accomplished using a mathematical algorithm. In an embodiment, the percent identity between two amino acid or nucleic acid sequences is determined using the Needleman and Wunsch (1970) algorithm which has been incorporated into the GAP program in the Accelrys GCG software package (available at http://www.accelrys.com/products/gcg/), using either a Blosum 62 matrix or a PAM250 matrix, and a gap weight of 16, 14, 12, 10, 8, 6, or 4 and a length weight of 1, 2, 3, 4, 5, or 6. The CDRs of the heavy chain (CDRH) and light chain variable domain (CDRL) are located at residues 27-38 (CDR1), residues 56-65 (CDR2) and residues 105-117 (CDR3) of each chain according to the IMGT numbering system (http://www.imgt.org; Lefranc MP, 1997, J, Immunol. Today, 18, 509). This numbering system is used in the present specification except where otherwise indicated. All publications, patents and patent applications cited herein, whether supra or infra, are hereby incorporated by reference in their entirety. The following examples illustrate the invention. Examples BA.2.86, a recently described sub-lineage of SARS-CoV-2 Omicron, contains a large number of mutations in the spike gene. It appears to have originated from BA.2 and is distinct from the XBB variants currently responsible for most infections. The global spread and plethora of mutations in BA.2.86 has caused concern that it may possess greater immune evasive potential, leading to a new wave of infection. Here the inventors examined the ability of BA.2.86 to evade the antibody response to infection using a panel of vaccinated or naturally infected sera and find that it shows marginally less immune evasion than XBB.1.5. The inventors located BA.2.86 in the antigenic landscape of recent variants and look at its ability to escape panels of potent monoclonal antibodies generated against contemporary SARS-CoV-2 infections. The inventors demonstrated, and provided a structural explanation for, increased affinity of BA.2.86 to ACE2, which may increase transmissibility. The majority of the human population is believed to have been exposed to SARS- CoV-2, by natural infection (771 million cases and 7 million deaths confirmed as of 27/9/23, but the actual numbers are likely much higher), and/or vaccination, often on multiple occasions. This herd immunity has put the SARS-CoV-2 genome under huge selective pressure to evade pre-existing immune responses, hence the abundance of variants. A particular hot spot for mutational change in SARS-CoV-2 is in the spike gene, encoding the spike protein (S). The characteristic spikes on the surface of coronaviruses are formed by trimers of S, linked to the virion through transmembrane helices at the C- terminus. S is made up of an N-terminal S1 domain, responsible for attachment to the host receptor angiotensin converting enzyme 2 (ACE2)², and a C-terminal S2 domain, which through conformational rearrangement executes fusion of host and viral membranes, allowing entry of viral RNA into the host cell cytoplasm, initiating the infectious cycle. S1 contains a string of rather small domains, including the N-terminal domain (NTD) and receptor binding domain (RBD). The RBD is positioned at the top of S and can adopt a range of conformational states, from a fully exposed “up” conformation, able to interact with ACE2, to a more hidden “down” conformation. At the tip of the RBD is a small 25 amino acid (aa) patch, the receptor binding motif, that forms a landing pad for ACE2. Characterization of panels of monoclonal antibodies (mAb) from previously infected donors, has allowed a detailed mapping of the antigenic determinants for potent virus neutralization, and enabled the generation of a number of mAb for therapeutic or prophylactic use. Antibodies binding to the so-called super-site in the NTD don’t antagonize interaction with ACE2, but can show potent neutralization; these antibodies and their function are poorly understood. The RBD is the binding site for a number of potent mAb, many of which bind on, or in close proximity to the ACE2 binding surface and block ACE2 interaction. Another group, characterized by mAb S309 bind distant to the ACE2 binding surface, in proximity to the N-linked glycan attached to N343; these do not block ACE2 interaction and may function to destabilize the S trimer. The NTD and RBD are hotspots for mutational change, either by substitution or, in the case of the NTD, the insertion or deletion of amino acid residues. For the NTD, it is likely that mutation is in part immune driven, with the majority of potent anti-NTD mAb being specific to a single or limited number of lineages. For the RBD, mutations can increase the affinity for ACE2, potentially giving the virus a transmission advantage. Mutations at the binding sites for neutralizing anti-RBD antibodies can lead to a reduction of the neutralizing titres of immune serum, promoting immune escape and enabling reinfection. Mutations of key residues in the ACE2 interaction surface can therefore act as a double-edged sword for the virus, potentially modulating ACE2 affinity at the same time as causing antibody escape. The first sequence for BA.2.86 was deposited on 13^th of August 2023 (EPI_ISL_18096761) from Israel and since then 379 sequences have been deposited from multiple countries. BA.2.86 contains 51 aa substitutions, 8 aa deletions, and 4 aa insertions compared to the ancestral Wuhan S sequence. It does not appear that BA.2.86 has arisen from the currently dominating strains related to XBB and the closest ancestor is BA.2 (Figure 1). The large jump from BA.2 (38 aa changes in S alone) and the lack of any intermediate sequences, has led to speculation that BA.2.86 may have emerged in an immunosuppressed individual chronically infected with BA.2. The emergence, global spread and the ability of BA.2.86 to cause outbreaks such as that reported in a care home in the UK with a 86.6% attack rate among residents, has led to concern that it may show increased immune escape and be poised to cause a new wave of infection. Here, the inventors characterised BA.2.86 using a panel of sera collected following natural infection or vaccination and demonstrate that it shows less antibody evasion than several other contemporary strains allowing the inventors to place BA.2.86 on an antigenic map. the inventors also looked at the ability of a panel of potent (against XBB.1.5) human mAb isolated following infection with contemporary SARS-CoV-2 strains to neutralize BA.2.86, showing that the majority of these potent mAb can still neutralize BA.2.86 and provide structural explanations for this cross-reactivity. However, these potent antibodies have focussed their footprints to a distinct epitope on the RBD where they are vulnerable to escape by mutation at residues 455 and 456. Finally, the inventors measured the affinity of BA.2.86 RBD for ACE2 and show a 2.2-fold increase in affinity compared to XBB.1.5, for which the inventors provided a structural solution. In summary, whilst the mutations acquired by BA.2.86 do not impart a step change in antibody escape, the increase in ACE2 affinity may give BA.2.86 a transmission advantage in coming months. Results The BA.2.86 lineage BA.2.86 has assembled a unique suite of mutations and appears to have evolved separately from the XBB sub-lineage of Omicron, which currently dominates infections world-wide. Compared to S from the ancestral Wuhan strain, there are 63 aa changes present in BA.2.86, with 51 substitutions, 8 deletions, and 4 insertions. There are hot spots of mutation in the NTD and RBD, known sites for the binding of potent antibodies. In the NTD there are 13 substitutions, 7 deletions and 4 insertions (7.9% change compared to Wuhan), and in the RBD 24 substitutions and 1 deletion (12.9% change compared to Wuhan) (Figure 1A-C). Of particular interest, is the deletion of Valine at position 483, which is a site of interaction with ACE2. A phylogenetic tree (Figure 1D) places BA.2.86 far distant from other Omicron lineages with its likely origin BA.2, which has not been a major circulating sub-lineage for more than a year, having been replaced by BA.4/5 in mid 2022. Compared to BA.2, there are 38 aa changes in BA.2.86 (29 substitutions, 5 deletions and 4 insertions; with 9 substitutions, 4 deletions and 4 insertions are in NTD and 12 substitutions and 1 deletion in RBD). There has been very extensive evolution of the virus from BA.2. The absence of any intermediate species in the BA.2.86 sub-lineage leads to speculation that it may have evolved over a long period in a chronically BA.2 infected immunosuppressed individual, where the accrual or multiple mutations and their potential admixture by viral recombination events has led to a virus fit to escape into the general population and spread globally. It is therefore interesting to note that changes at all but one (insertion MPLF at residue 16) of the mutated residues, despite their independent evolution, have been observed in other contemporary variants derived from BA.2, showing extreme evolutionary convergence (Table 6). Deletions in the ACE2 binding surface are rare but deletion of V483 was seen in some sequences in 2022 and there have been a total of 2897 sequences deposited since the start of the pandemic. Of the mutations in the RBD, five show more than one mutation in the amino acid codon: V445H, L452W, V483del, E484K and F486P. Neutralisation of BA.2.86 by vaccine serum The inventors constructed a panel of pseudotyped lentiviruses expressing the S gene of a series of variants from Omicron sublineages, BA.2, BA.4/5, XBB.1.5, XBB.1.5.10 (XBB.1.5 + F456L), XBB.1.5.70 (XBB.1.5 +L455F +F456L), and BA.2.86. Neutralisation assays were performed using serum collected 18 months following a third dose of vaccine (Pfizer-BioNtech, or Moderna, n=17), and 6 months after a fourth dose of vaccine (Bivalent Pfizer-BioNtech (Wuhan/BA.1) or Bivalent Moderna (Wuhan/BA.1), (n=23) (Table 7). For samples obtained 18 months after triple vaccination, neutralization titres of BA.2.86 show 13.4-fold reduction compared with BA.2 (p < 0.0001) and 8.0-fold reduction compared with BA.4/5 (p < 0.0001), but are increased 1.3-fold (p = 0.0425), 1.7- fold (p = 0.0083) and 2.2-fold (p = 0.0024) compared to XBB.1.5, XBB.1.5.10 and XBB.1.5.70, respectively (Figure 2A). Neutralization titres of the samples collected 6 months after a fourth bivalent dose of vaccine showed a similar trend, BA.2.86 titres are reduced 10.4-fold (p < 0.0001) and 4.4-fold (p < 0.0001) and increased 2.2-fold (p < 0.0001), 2.5-fold (p < 0.0001) and 4.6- fold (p < 0.0001) compared with BA.2, BA.4/5, XBB.1.5, XBB.1.5.10, and XBB.1.5.70, respectively (Figure 2B). Neutralization of BA.2.86 by sera collected following natural infection Breakthrough BA.2 serum samples were taken from vaccinated volunteers ^ 12 days from symptom onset (median 29 days; n=19) (Figure 2C). The neutralisation titres of BA.2.86 are reduced 10-fold (p < 0.0001) and 5.6-fold (p < 0.0001) compared with BA.2 and BA.4/5, respectively, but 1.3-fold (p = 0.2753), 2.8-fold (p < 0.0001) and 3.2-fold (p < 0.0001) higher than XBB.1.5, XBB.1.5.10 and XBB.1.5.70, respectively. BA.4/5 serum samples taken from 11 individuals (all but one vaccinated) more than 14 days (median = 38 days) (Figure 2D) post BA.4/5 infection, show more modest reductions in neutralisation; BA.2.86 titres are reduced 4.3-fold (p = 0.0010) and 3.5-fold (p = 0.0010) and increased 1.7-fold (p = 0.0029), 3.5-fold, (p = 0.0020) and 4.8-fold (p = 0.0010) compared to BA.2, BA.4/5, XBB.1.5, XBB.1.5.10 and XBB.1.5.70, respectively. A set of recent breakthrough infection samples obtained from 19 vaccinated volunteers who had documented infections with several variants (Table 8) between August 2022 and February 2023, follow the same trend (Figure 2E). BA.2.86 titres show 7.7-fold (p < 0.0001), 4.8-fold (p < 0.0001) reduction and 1.4-fold, 2.1-fold and 2.2-fold increase compared to BA.2, BA.4/5, XBB.1.5, XBB.1.5.10, and XBB.1.5.70, respectively. In summary, neutralization of BA.2.86 by vaccinated or naturally infected serum is reduced compared with BA.2 and BA.4, but modestly increased compared with XBB.1.5, XBB.1.5.10, and XBB.1.5.70. The concordant results in all groups may result from immune imprinting in the participants, all but one of whom had been vaccinated in the early phase of the pandemic (Figure 2F). Antigenic cartography of BA.2.86 Neutralization data presented in Figure 2A-F were merged with a library of neutralization data generated from vaccinated cases and from previous infection with ancestral virus, Alpha, Beta, Gamma, Delta and BA.1, and an antigenic map was produced using a previously reported method (Figure 2G). When Omicron BA.1 first emerged, it was placed far distant on the antigenic map from the previous variants Wuhan, Alpha, Beta, Gamma and Delta. The current map demonstrates the scale of evolution of SARS-CoV-2 since the emergence of BA.1 and BA.2. The evolution of XBB and its sublineages have pushed the antigenic distance further still, with XBB.1.5.10 and XBB.1.5.70 being the most distant of the lineages studied to date. As expected from the neutralization data presented in Figure 2A-E, BA.2.86 occupies an intermediate space amongst contemporary variants. Neutralization by a panel of potent mAb generated from BA.2 infected cases Following the BA.2 wave of infection in early 2022 the inventors generated a panel of 25 potent human mAb (IC50 < 100ng/ml) from infected volunteers (as disclosed in Dijokaite-Guraliuc et al., 2023 Cell Reports 42, 112271; and GB 2215904.0 and GB 2300873.3). All these mAb potently cross neutralized the early pandemic strain (Victoria) and as all participants in this study had been vaccinated, the inventors speculated that these potent BA.2 neutralizing mAb may have been generated from memory B cell clones laid down in the initial response to vaccination. Strikingly, the neutralization of all 25 mAb was dramatically reduced against BA.2.86, with complete knock out of activity of 22/25 mAb (Figure 3A). The inventors have previously mapped the binding sites of these 25 mAb either by direct crystallographic determination, or by imputing their binding sites using a BLI competition mapping technique (Figure 3B), with sentinel mAb with structurally determined coordinates, which gave a precision of ~8Å. This, together with structural information for some BA.2 mAbs (Figure 7), allows the inventors to propose which amino acid changes lead to the failure of each antibody, see Figure 3A. Neutralization of BA.2.86 by a panel of mAb potently neutralizing XBB.1.5 The inventors generated a panel of monoclonal antibodies from vaccinated individuals who suffered BA.4, BA.5.1, or XBB.1.5 infections. Memory B cells from 6 breakthrough infection cases were stained with XBB.1.5 RBD. In total, 127 RBD-specific antibodies were recovered and following RT-PCR mAb were expressed and tested in neutralization assays against XBB.1.5. Only 10 mAb with IC50 neutralization titres <100ng/ml to XBB.1.5 were selected for further study (Table 9). All mAb, except XBB-5 and XBB-7, showed potent cross neutralization of BA.2 and BA.4/5 (Figure 4A, B and Table 5). However, neutralization of XBB.1.5.10 and XBB.1.5.70, containing F456L and L455F + F456L mutations in the RBD respectively, were knocked out or reduced >10-fold compared to neutralization of XBB.1.5 in 7/10 of the potent mAb. The focus of potent mAb from recently infected individuals, on an epitope containing residues 455 and 456, on the back of the left shoulder of the RBD (Figure 4C), was likely because mAb that bind to other epitopes on the RBD, have been knocked out by the numerous mutations in successive SARS-CoV-2 variants, whereas the 455/456 region has remained more or less unscathed until recently (Figure 4C). It is notable that EG.5.1 (F456L) is currently the dominant Omicron sub-lineage in many regions such as the USA, China and Japan, accounting for more than 25% of global cases. Interestingly, BA.2.86 does not contain mutations at residues 455 or 456 and the neutralization titres of the XBB mAb are comparable to those against XBB.1.5, with only XBB-4 showing >10-fold reduction in titre against BA.2.86 compared to XBB.1.5. The absence of the mutations at residue 455 and 456 in BA.2.86 likely explains the higher neutralization titres against vaccine and naturally infected sera compared to XBB.1.5.10 and XBB.1.5.70. Finally, the inventors looked at the neutralization titres of mAb developed for clinical use against BA.2.86, the activity of all of them was completely knocked out, including S309/sotrovimab which had maintained some activity against previously encountered variants apart from BN.1 (Figure 4D). It is likely that the K356T mutation in BA.2.86 abolishes the neutralization ability of S309, since this residue makes a salt bridge to residue E108 and hydrophobic contacts with F106, both in the H3 CDR of S309 (Figure 4E). Affinity of BA.2.86 for ACE2 The inventors measured the affinity of BA.2.86 RBD for ACE2 using surface plasmon resonance (SPR). Biotinylated ACE2 was attached to a streptavidin-immobilised CM5 sensor chip (Cytiva) and soluble RBD was flowed over (Figure 4F). KD for ACE2/BA.2.86 RBD was 8.3 nM, 2.2-fold and 1.7-fold higher than XBB.1.5 and Beta RBDs respectively. The affinity of Beta RBD for ACE2 was itself 19-fold higher than the inventors previously measured for ancestral Wuhan RBD (Figure 4G) and the increased affinity compared to XBB.1.5 may give BA.2.86 a transmission advantage against XBB.1.5 derived strains of SARS-CoV-2 which currently dominate infections globally. Structural characterization of BA.2.86 The inventors determined the structure of the soluble trimeric S protein of BA.2.86 (in complex with XBB-7, see below] (Figure 5). The RBD is rather mobile and not well ordered, however it is possible to model and refine the structure of the RBD and it is clear that the numerous mutations and the deletion of residue 483 do not introduce major changes (RMSD compared to BA.2.75 RBD for 188 RBD Cα 0.56 Å, Figure 5A,B). The 483 deletion causes some changes in the loop but the major contact region with ACE2 (RBM) is not significantly changed, likely caused by the disulphide between residues 480 and 488 locking the structure in place (Figure 5B). Structure of ACE2 complexed with BA.2.86 trimeric spike The cryo-EM structure of the complex was determined at a nominal resolution of 3.7 Å resolution. Previous analyses report one RBD bound, sometimes with partial occupancy of a second, the inventors see 2 RBDs in the up configuration with ACE2 attached, but neither of which is well ordered, consistent with flexibility of the RBDs. Nevertheless, using local refinement, the inventors were able to model one ACE2/RBD complex using the BA.2.86 RBD structure from the XBB-7 complex described below and the ACE2 model from the complex with BA.2.75 RBD (Figure 5A). Given the limited resolution the inventors were able to model only as rigid bodies. Comparing with the complex structure for the BA.2.75 (as a representative of earlier variants, Figure 5B) the inventors observe a small tilt of the ACE2. The effect is to move the C-terminal end of the first helix of ACE2, responsible for major interactions with the right shoulder of the RBD, slightly away from the RBD. This may be due to the loss of hydrophobic interactions due to the F486P mutation in the BA.2.86 RBD (Figure 5B) and is unlikely to contribute to the increased affinity for ACE2. However, inspection of the electrostatic properties of the ACE binding surface suggests that the major driver for increased affinity, compared to the Wuhan strain, is electrostatic complementarity between BA.2.86 RBD and ACE2 (Figure 5C). Indeed, several of the mutations introduced into BA.2.86 have previously been identified as enhancing affinity notably N440K, G446S, E484K and Y505H. Finally, the inventors note that the affinity for BA.2.86 RBD and ACE2, might be further enhanced by the flexibility of the RBDs, possibly improving the presentation of the ACE2 binding site in the context of virus associated trimeric S protein. Structures of XBB antibodies in complex with RBD and S trimer The complex of XBB-2 Fab with Delta RBD and nanobody C1 was determined at 2.3 Å resolution by crystallography (Figure 6A,D,E). The antibody belongs to the IGHV3- 53 variable gene family and binds in the pose characteristic of most of this family at the back of the RBD. While many of the antibodies belonging to this public gene family were knocked out by variation in the RBD, XBB-2 has structural differences, notably in the light chain variable regions, that allow it to effectively neutralize XBB. Despite contacting residues 455 and 456 in the RBD this antibody can still neutralize viruses mutated at these residues, although at much reduced potency (Figure 4B). It is notable that 5/10 of the potent XBB mAb belong to the public IGHV3-53/66 gene family and are likely to bind in a similar position to XBB-2, indeed XBB-9 shows potent neutralization of all variants tested. The complex of XBB-6 Fab with Delta RBD and Beta 49 Fab was determined at 3.7 Å resolution by crystallography (Figure 6B,F,G,H). XBB-6 belongs to the same gene family as Omi-42 (IGHV3-9), and binds in a very similar pose, also at the back of the RBD, in a similar orientation (22° rotation) to XBB-2, but with a shift of ~7.5 Å towards the back of the left shoulder. This antibody uses RBD residues 455 and 456 for binding, with the interactions being much stronger than for XBB-2, and it is knocked out when these residues are mutated. XBB-7 is more cross-reactive than XBB-2 and XBB-6, with little reduction in potency for RBDs bearing mutations at 455 and 456, however its potency is reduced ~8x against BA.2.86. The inventors determined the structure of its Fab in complex with the BA.2.86 S trimer by cryo-EM at 3.6 Å resolution (Figure 6C,I,J,K). This antibody belongs to the IGHV3.7 gene family and also binds at the back of the RBD in a similar orientation to XBB-2 but is shifted towards the right shoulder. Only 3 hypervariable loops form contacts with the RBD, H3, H1 and L1. The heavy chain CDR3 loop is unusually long (24 residues) and crosses over the top of the neck to the front of the RBD. RBD residue 456 contacts a proline from H3, leading to 4-fold reduction in potency for the F456L mutation in XBB.1.5.10. However, the further adjacent mutation, L455F, seen in XBB.1.5.70 compensates for this, so there is little impact on potency. Discussion The emergence of BA.2.86 has raised concern that it may possess a more immune evasive phenotype than currently circulating strains. The results reported here and those from others (Yang et al., 2023, Lancet Infect Dis.10.1016/S1473-3099(23)00573-X; Wang et al., 2023, bioRxiv. https://doi.org/10.1101/2023.09.24.559214), indicate that this is not the case. A variety of vaccine and naturally infected sera show very similar neutralization profiles, with BA.2.86 being marginally easier to neutralize than XBB.1.5 and considerably easier to neutralize than XBB.1.5.10, which has an identical RBD to the currently circulating EG.5.1 strain. The donors of sera in the UK were largely multiply vaccinated healthcare workers and the highly related neutralization profiles that each group of sera displayed may result from similar imprinting of individual antibody responses, it is possible that sera from other areas, particularly where vaccine use has been less prevalent, may differ (Figure 2F). The inventors did not have access to many recently infected XBB cases, but Moderna have reported good neutralization of BA.2.86, following a boost with their most recent XBB.1.5 containing mRNA vaccine. However, the inventors’ analysis of the panel of potent mAb produced from cases infected with contemporary strains show a remarkable concentration of the response to an epitope on the back of the left shoulder of the RBD (8/10 mAb). This epitope, which was rarely used in responses made early in the pandemic, is exemplified by mAb Omi-42, that the inventors isolated from a volunteer following BA.1 infection (Huo et al., 2022, Cell Discov 8, 119.10.1038/s41421-022-00482-3). The epitope overlaps residues 455 and 456, which are mutated in the most recently circulating variants XBB.1.5.10, AG.1.5 (F456L) and XBB.1.5.70, which contains the so-called “flip mutations” L455F + F456L. The activity of 7/10 potent XBB mAb were either knocked out or severely impaired when 455 and 456 were mutated. Structural analysis of three of these mAb confirm binding to the epitope at the back of the left shoulder and direct interaction with 455/456 (Figure 6). The activity of XBB-9 a VH3-53 mAb, which likely binds to a similar epitope on the left shoulder of the RBD, was not affected by the 455/456 mutations. Although ∆V383 has been seen before in SARS-CoV-2 sequences, the deletion of residues in the ACE2 binding surface of RBD has been rare. Such a change might be thought likely to cause epistatic knock-on effects, reshaping the ACE2 interaction surface in a more profound way than simple amino acid substitution. In practice the structural changes are minor and localized, the presence of a disulphide bond close to ∆V383 appears to lock the loop, limiting the propagation of conformational change (Figure 5B). Despite the abundance of mutations within the ACE2 footprint (10 out of 25 residues mutated compared to Wuhan) the inventors demonstrated that BA.2.86 has high affinity for ACE2 (a 2.2-fold increase compared to XBB.1.5). Structural analysis shows a minor change in binding mode for ACE2 compared to previous variants but suggests that the increase in affinity is improved electrostatic complementarity. Looking at a succession of strains appears to show that ACE2 affinity gains such as those seen with Alpha and Beta were lost when a strain such as Omicron, arises, carrying significant mutational burden, exemplified by drop of affinity seen in the transition from Delta to Omicron. Binding is then recovered with the transition to BA.2.75 (Figure 4G). These changes may not be by chance, most mutations leading to antibody escape will come at a cost to ACE2 affinity, which itself may compromise transmission of the virus, driving selection of new mutations to restore ACE2 affinity, which then gives an ACE2 affinity with sufficient head room to enable the selection of mutations to further escape as seen in the Delta to Omicron transition. In contrast BA.2.86 does not achieve greater escape than several other contemporary viruses but has achieved strong ACE2 binding despite a considerable mutational burden. Interestingly most mutations to BA.2 seen in BA.2.86 have also been acquired by other Omicron sub-lineages such as BA.4/5 and XBB, suggesting coevolution, presumably in response to shared immune selective pressures. The lack of intermediary viruses makes it likely that BA.2.86 has evolved sequentially in a chronically infected individual. It is noteworthy that other variants such as Beta and Omicron first emerged in Southern Africa, which may be the origin of BA.2.86. The high prevalence of HIV and of cases not on antiretroviral treatment can provide a substrate for chronic infections, which have been observed for upwards of a year, during which time considerable viral evolution has been documented to occur. It seems possible that in some immunosuppressed individuals, the immune response is perfectly poised to put pressure on the virus to evolve, but insufficient to clear infection. In such individuals, the antibody response may continue to evolve in response to viral mutational change, in effect leading to a long-term bootstrapping of viral and antibody evolution, allowing the generation of far distant sequences, until a point where a virus is produced which is fit to escape into the immunocompetent environment. Indeed BA.2.86 can escape from all the potent mAb the inventors generated from BA.2 infected cases (Dijokaite-Guraliuc et al., 2023 Cell Reports 42, 112271) and appears to possess considerable resistance to BA.4 sera (Dijokaite-Guraliuc et al., 2022, Cell Discov 8, 127.10.1038/s41421-022-00493-0). In summary, the inventors demonstrated that BA.2.86 has not developed an extreme antibody escape phenotype, however, the increase in ACE2 affinity may give the virus a transmission advantage. Whether this will allow BA.2.86 to become the dominant circulating strain will become clear in the next weeks and months. An XBB.1.5 based mRNA vaccine should give some protection against BA.2.86 infection, but the results suggest that this might focus responses to the RBD epitope containing residues 455 and 456, increasing pressure on BA.2.86 to acquire mutations in these residues such as the F456L mutation seen in currently circulating EG.5.1, leading to effective escape. On this final point, it is noteworthy that 9 deposited sequences of BA.2.86 contain an L455S mutation. Methods Bacterial Strains and Cell Culture HEK293T (ATCC CRL-11268) cells were cultured in DMEM high glucose (Sigma-Aldrich) supplemented with 10% FBS, 1% 100X Mem Neaa (Gibco) and 1% 100X L-Glutamine (Gibco) at 37 °C with 5% CO2. To express spike, RBD and ACE2, Expi293F cells (Thermo Fisher Scientific) were cultured in Expi293 Expression Medium (Thermo Fisher Scientific) at 37 °C for transfection. Human mAbs were also expressed in HEK293T (ATCC CRL-11268) cells cultured in FreeStyle 293 Expression Medium (ThermoFisher, 12338018) at 37 °C with 5% CO2. E.coli DH5α bacteria were used for transformation and large-scale preparation of plasmids. A single colony was picked and cultured in LB broth at 37 °C at 200 rpm in a shaker overnight. Sera from BA.2 infected cases, study subjects Healthcare workers with BA.2 infection were co-enrolled. All individuals had PCR-confirmed symptomatic disease and sequence confirmed BA.2 infection through national UKHSA sequencing data. A blood sample was taken following consent at least 12 days after PCR test confirmation. Clinical information including vaccination history, times between symptom onset and sampling and age of participant was captured for all individuals at the time of sampling. Sera from BA.4/5 infected cases and breakthrough infections in the past 12M, study subjects Individuals with omicron BA.4, BA.5, BA.2.73, BA.5.1, BA.5.2, XBB.1.5, BE.1, CH.1.1, CH.1.1.2 and BQ.1.1 were co-enrolled. Diagnosis was confirmed through reporting of symptoms consistent with COVID-19, hospital presentation, and a test positive for SARS-CoV-2 using reverse transcriptase polymerase chain reaction (RT-PCR) from an upper respiratory tract (nose/throat) swab tested in accredited laboratories and lineage sequence confirmed through national reference laboratories in the United Kingdom. A blood sample was taken following consent at least 14 days after PCR test confirmation. Clinical information including severity of disease (mild, severe or critical infection according to recommendations from the World Health Organisation) and times between symptom onset and sampling and age of participant was captured for all individuals at the time of sampling. Sera from vaccinees V3 + 18M and V4 + 6M vaccine serum were obtained from volunteers who had received three doses of the Pfizer/BioNTech vaccine, Moderna vaccine or Oxford/AstraZeneca vaccine, and volunteers who had received three or four doses of Pfizer/BioNTech vaccine or Oxford/AstraZeneca vaccine before receiving a fourth (or fifth, 1 volunteer only) dose of Pfizer/BioNTech or Moderna bivalent vaccine (Table 7). Vaccinees were Health Care Workers (previous infection history is shown in Table 8) and were enrolled. Isolation of XBB.1.5 RBD-specific single B cells by FACS XBB.1.5 RBD-specific single B cell sorting was performed as previously described. Briefly, 6 PBMCs of breakthrough infection (1 BA.4 infection, 1 BA.5.1 infection, 2 XBB.1.5 infection and 2 unknown infection) who were infected by BA.4, BA.5.1 or XBB.1.5 were stained with LIVE/DEAD Fixable Aqua dye (Invitrogen). Cells were then incubated with CD3-FITC, CD14-FITC, CD16-FITC, CD56-FITC, IgM-FITC, IgA-FITC, IgD-FITC, IgG-BV786 and CD19-BUV395, along with Strep-MAB-DY549 to stain the twin strep tag of the XBB.1.5 SD1-RBD protein, and anti-His-APC to stain the 6 × His tag of the XBB.1.5 RBD. IgG+ memory B cells were gated as CD19+, IgG+, CD3-, CD14-, CD56-, CD16-, IgM-, IgA- and IgD-, and XBB.1.5 SD1-RBD and XBB.1.5 RBD double positive was further selected, and single cells were sorted into 96-well PCR plates with 10 μL of catching buffer (Tris, Nuclease-free-H2O and RNase inhibitor). Plates were briefly centrifuged at 2000ⅹg for 1 min and left on dry ice before being stored at -80℃. Antigenic mapping Antigenic mapping of omicron was carried out using a previously described method (Tuekprakhon et al. (2022). Cell 185, 2422-2433 e2413.). In short, coronavirus variants were assigned coordinates (initially chosen randomly) whereby the distance between two points indicates the base drop in neutralization titre. Each serum was assigned a strength parameter which provided a scalar offset to the logarithm of the neutralization titre. These starting parameters were refined to match predicted neutralization titres to observed values. This was repeated and the final map was the average of superimposed positions from 20 separate runs. The positions of the variants were plotted for display. Previously the 3D coordinates were refined. For these data the inventors found that the match of predicted and observed titres was almost equally good for a 2D model, and so the simpler 2D model in presented here. Cloning and expression of XBB.1.5 RBD-specific human mAbs XBB.1.5 RBD-specific human mAbs were cloned and expressed as described previously (Dejnirattisai et al. (2021). Cell 184, 2183-2200 e2122). Briefly, genes for Ig IGHV, Ig Vκ and Ig Vλ were recovered from positive wells by RT-PCR. Genes encoding Ig IGHV, Ig Vκ and Ig Vλ were then amplified using Nested-PCR by a cocktail of primers specific to human IgG. PCR products of HC and LCs were ligated into the expression vectors of human IgG1 or immunoglobulin κ-chain or λ-chain by Gibson assembly. For mAb expression, plasmids encoding HCs and LCs were co-transfected into a HEK293T cell line by PEI-transfection, and supernatants containing mAbs were collected and filtered 4–5 days after transfection, and the supernatants were purified. Pseudovirus plasmid construction and lentiviral particles production Pseudotyped lentivirus expressing SARS-CoV-2 S proteins from BA.1, BA.2, BA.4/5, and XBB.1 were constructed as described previously (Nutalai et al. (2022) Cell 185, 2116-2131; Tuekprakhon et al. (2022) Cell 185, 2422-2433 e2413; Dijokaite-Guraliuc et al. (2022). Cell Discov 8, 127.10.1038/s41421-022-00493-0). The same method was used to construct XBB.1.5 by introducing F486P mutation into XBB.1, XBB.1.5.10 by introducing F456L mutation into XBB.1.5, and XBB.1.5.70 by adding L455F into XBB.1.5.10. Plasmid to create BA.2.86 PV was custom synthesized by Integrated DNA Technologies based on the wild-type SARS-CoV-2 BA.2.86 (EPI_ISL_18110065) and cloned into pcDNA3.1 plasmid. This plasmid carries S gene and was used for generating pseudoviral particles together with the lentiviral packaging vector and transfer vector encoding luciferase reporter. A BA.2.86 plasmid containing the following mutations was produced: ins16MPLF, T19I, R21T, L24del, P25del, P26del, A27S, S50L, H69del, V70del, V127F, G142D, Y144del, F157S, R158G, N211del, L212I, V213G, L216F, H245N, A264D, I332V, G339H, K356T, S371F, S373P, S375F, T376A, R403K, D405N, R408S, K417N, N440K, V445H, G446S, N450D, L452W, N460K, S477N, T478K, N481K, V483del, E484K, F486P, Q498R, N501Y, Y505H, E554K, A570V, D614G, P621S, H655Y, I670V, N679K, P681R, N764K, D796Y, S939F, Q954H, N969K, P1143L. All the constructs were sequence confirmed. Pseudoviral neutralization test The pseudoviral neutralization test has been described previously (Liu et al. (2021). Cell, Host and Microbe 30, 53-68). Briefly, the neutralizing activity of potent monoclonal antibodies generated from donors who had recovered from BA.1 and BA.2 infection were tested against BA.1, BA.2, BA.4/5, XBB.1.5, XBB.1.5.10, and XBb.1.5.70. Four-fold serial diluted mAbs were incubated with pseudoviral particles at 37°C, 5% CO₂ for 1 hr. Stable HEK293T/17 cells expressing human ACE2 were then added to the mixture at 1.5 × 10⁴ cells/well.48 hr post infection, culture supernatants were removed and 50 μL of 1:2 Bright-Glo TM Luciferase assay system (Promega, USA) in 1 × PBS was added to each well. The reaction was incubated at room temperature for 5 mins and firefly luciferase activity was measured using CLARIOstar® (BMG Labtech, Ortenberg, Germany). The percentage neutralization was calculated relative to the control. Probit analysis was used to estimate the dilution that inhibited half maximum pseudotyped lentivirus infection (PVNT50). To determine the neutralizing activity of convalescent plasma/serum samples or vaccine sera, 3-fold serial dilutions of each sample were incubated with pseudoviral particles for 1 hr and the same strategy as mAb was applied. Construction of trimeric spike of SARS-CoV-2 BA.2.86 Expression plasmid of BA.2.86 spike was constructed encoding for human codon- optimized sequences from wild-type SARS-CoV-2 (MN908947) and BA.2.86 (EPI_ISL_18110065). Fragments were cloned in pHLsec vectors downstream of the chicken β-actin/rabbit β-globin hybrid promoter and followed by a T4 fibritin trimerization domain, an HRV 3C cleavage site, a His-8 tag and a Twin-Strep-tag at the C terminus as previously reported by Wrapp et al., 2020, bioRxiv.10.1101/2020.02.11.944462. Mutations coding for stabilizing proline residues and to eliminate putative furin cleavage sites were inserted in BA.2.86 sequence as follows: RRAR > GSAS (aa 682-685) and KV > PP (aa 986-987). Spike includes following mutations: ins16MPLF, T19I, R21T, L24del, P25del, P26del, A27S, S50L, H69del, V70del, V127F, G142D, Y144del, F157S, R158G, N211del, L212I, V213G, L216F, H245N, A264D, I332V, G339H, K356T, S371F, S373P, S375F, T376A, R403K, D405N, R408S, K417N, N440K, V445H, G446S, N450D, L452W, N460K, S477N, T478K, N481K, V483del, E484K, F486P, Q498R, N501Y, Y505H, E554K, A570V, D614G, P621S, H655Y, I670V, N679K, P681R, N764K, D796Y, S939F, Q954H, N969K, P1143L. Spike fragments were custom synthesized by Integrated DNA Technologies and cloned into pHLsec vector as previously described (Dejnirattisai et al. (2021) Cell 184, 2183-2200 e2122; Supasa et al. (2021) Cell 184, 2201-2211 e2207; Zhou et al. (2021) Cell 184, 2348-2361 e2346). Spike sequence was verified by Sanger sequencing. Cloning of RBDs Gene fragment encoding RBD was ordered from Integrated DNA Technologies. This gene fragment comprises a 5’ tag (5’- GTTGCGTAGCTGAAACCGGT-3’), DNA sequence encoding a 6 × His tag, human codon-optimized DNA sequence of RBD BA.2.86 (332-526aa) and a 3’ tag (5’- AACAGCACCTCAAGGGTACC-3’). Vector pHR-CMV- TetO2_IRES-EmGFP was cut with restriction enzymes AgeI and KpnI and was assembled with the gene fragment using In-Fusion cloning. E.coli DH5α bacteria were used for transformation of plasmids and single colonies were picked and cultured in LB broth. Sequence of extracted plasmid was confirmed by Sanger sequencing. Constructs of other RBD proteins used in the Examples are as previously described (Dejnirattisai et al. (2021) Cell 184, 2183-2200 e2122; Supasa et al. (2021) Cell 184, 2201- 2211 e2207; Zhou et al. (2021) Cell 184, 2348-2361 e2346). Production of proteins Protein expression and purification were as reported previously (Dejnirattisai et al. (2021) Cell 184, 2183-2200 e2122; Zhou et al. (2021) Cell 184, 2348-2361 e2346). Briefly, Twin-strep tagged BA.2.86 spike was transiently transfected in HEK293T cells and purified with Strep-Tactin XT resin (IBA lifesciences). Purified protein was validated by SDS-PAGE and concentrated using a 100 kDa Amicon Centrifugal Filter. Plasmid encoding RBD was transiently transfected into Expi293F cells. Four days after transfection, the conditioned medium was harvested, filtered and buffer-exchanged using QuixStand benchtop system (Amersham Biosciences). The sample was purified with a 5 mL HisTrap nickel column (Cytiva) and further polished using a Superdex 75 HiLoad 16/60 gel filtration column (Cytiva). SDS-PAGE was used to validate the protein and protein was concentrated using a 10 kDa Amicon Centrifugal Filter. Surface Plasmon Resonance All SPR experiments were carried out at 37 °C on a Biacore T200 system using HBS-EP+ buffer (Cytiva). Biotinylated ACE2 (19-615aa)-Avi was captured using a streptavidin-immobilised CM5 sensor chip (Cytiva). The final capture level was 100 RU. A 2-fold serial dilution of seven concentrations of different RBDs starting at 320 nM was used to pass over the immobilized ACE2-biotin. All runs were reference and blank subtracted and normalised against the baseline RU levels prior to injection of the RBD analytes. The SPR data were fitted using the curve fitting “one site – specific binding” equation in GraphPad Prism (version 10.0.3) to derive the equilibrium dissociation constant (KD) values. The R2 of all fits were > 0.95. IgG mAbs and Fabs production AstraZeneca and Regeneron antibodies were provided by AstraZeneca, Vir, Lilly and Adagio antibodies were provided by Adagio, LY-CoV1404 was provided by LifeArc. For the in-house antibodies, heavy and light chains of the indicated antibodies were transiently transfected into 293T cells and antibody purified from supernatant on protein A as previously described ⁹. Fabs were digested from purified IgGs with papain using a Pierce Fab Preparation Kit (Thermo Fisher), following the manufacturer’s protocol. Crystallization, X-ray data collection and structure determination Delta-RBD was deglycosylated with Endoglycosidase F1 before used for crystallization. Ternary complexes of Delta-RBD/XBB-2/NbC1 and Delta-RBD/XBB- 6/Beta49 were made by mixing proteins together in a 1:1:1 molar ratio, with a final concentration of 11 mg mL^-1 and 7 mg mL^-1, separately. Screening of crystals was set up in Crystalquick 96-well X plates (Greiner Bio-One) with a Cartesian Robot using the nanoliter sitting-drop vapor-diffusion method, with 100 nL of protein plus 100 nL of reservoir in each drop, as previously described⁴³. Crystals of Delta-RBD/XBB-2/NbC1 were obtained from Hampton Research PEGRx condition 2-27, containing 2% (v/v) 1,4- Dioxane, 0.1 M Tris pH 8.0 and 15% (w/v) PEG 3350. Crystals of Delta-RBD/XBB- 6/Beta49 were obtained from Hampton Research PEGRx condition 1-40, containing 0.1 M citric acid pH 3.5 and 28% (w/v) PEG 8000. Crystals were mounted in loops and dipped in solution containing 25% glycerol and 75% mother liquor for a second before being frozen in liquid nitrogen. Diffraction data were collected at 100 K at beamline I03 of Diamond Light Source, UK, using the automated queue system that allows unattended automated data collection (https://www.diamond.ac.uk/Instruments/Mx/I03/I03-Manual/Unattended-Data- Collections.html).3600 diffraction images of 0.1º each were collected for each data set. Data were automatically processed with Xia2-dials. Each of the structures was determined using molecular replacement with Phaser and a model of the inventors’ previously determined RBD/Fab structures that has maximum sequence identity with the current structure (Dejnirattisai et al. (2021). Cell 184, 2183-2200 e2122; Liu et al. (2021) Cell, Host and Microbe 30, 53-68; Nutalai et al. (2022) Cell 185, 2116-2131; Dijokaite-Guraliuc et al. (2023). Cell Rep 42, 112271). Model rebuilding is done with COOT and refinement with Phenix. Due to the low resolution of Delta-RBD/XBB-6/Beta-49 data set, reference model restraints were applied in the refinement. Data collection and structure refinement statistics are given in Table 10. Structural comparisons used SHP and figures were prepared with PyMOL (The PyMOL Molecular Graphics System, Version 1.2r3pre, Schrödinger, LLC). Cryo-EM Grid Preparation A 3 μL aliquot of S ~1.2 µm with fab (1:6 molar ratio) was prepared, aspirated and almost immediately applied to a freshly glow-discharged Cflat 2/1-200 mesh holey grid (Protochips, supplied by Molecular Dimensions) at high intensity, 20 s, Plasma Cleaner PDC-002-CE, Harrick Plasma. Excess liquid was removed by blotting for 5 s with a force of -1 using vitrobot filter paper (grade 595, Ted Pella Inc.) at 4.5 ºC, 100 % reported humidity prior plunge freezing into liquid ethane using a Vitrobot Mark IV (Thermo Fisher). Cryo-EM Data collection BA.2.86 spike with XBB-7 fab and ACE2 Data were collected in EER format using EPU on a 300 kV Titan Krios microscope equipped with a Falcon-IVi detector and selectrisX energy filter using EPU software (Thermofisher) and employing 50 ^m C2, 100 ^m objective apertures (Table 6). In both cases, a total dose of 50 e/Ų was applied and movies recorded at 165 kX magnification, corresponding to a calibrated pixel size 0.7303 Å/pix and multiple shots per hole (9-10) were recorded. CryoEM data analysis Collected movies were 4-times binned and pre-processed (motion, CTF correction and blob particle picking) on the fly using the cryoSPARCv4.3.1 live. Movies were ‘cleaned’ using the live interface based on CTF estimation, defocus estimates, total motion and ice thickness. XBB-7 A total of 9664 movies were processed from which 524,958 particles were initially picked, which were filtered by 2D classification with 250 classes and a batch size of 200. Good classes, bearing clear secondary structure, were then selected, corresponding to 168,720 particles showing a variety of orientations. Particles were then aligned using a map generated from ab initio processing of this good subset before heterogenous refinement into three classes. From heterogeneous refinement, 147389 particles fell into a class that was well aligned and resolved. This set was then un-binned and refined. Although clearly only one ‘upwards’ RBD was decorated with fab, and the non-uniform refined structure was globally high resolution (2.6 Å GSFSC 0.143 reported), density for the RBDs and RBD/fab was extremely poor. To improve on this a series of 3D classifications and local refinements were trialled to get a better view of Fab/RBD interface. It was found that a small number of particles were clearly decorated with two fabs (ca.1.5 %), some with one relatively better resolved Fab and one potentially upwards RBD decorated with fab (33 %) but the better resolved had more clearly just one Fab bound (ca.40%). For the best strategy, 3D classification without alignment into eight classes with a focussed mask around the top, i.e. S1/XBB-7 portion of the spike was performed. Subsequent refinement of the separated particles did not help resolve the RBDs/ XBB-7 sufficiently for model building. The best subset, corresponding to 75021 particles was, therefore, locally refined twice, focussing on the best resolved XBB-7/RBD, resulting in a final reconstruction to 3.6 Å reported resolution (GSFSC, 0.143 CryoSPARC) with a bfactor of -77 Ų. ACE2 Akin to above, 9818 movies were collected with 504319 initially picked particles, which were then sorted by 2D classification, where 128,404 particles, in classes showing secondary structural detail and a variety of views were selected. Initial 3D processing via heterogenous refinement using three ab-initio generated volumes followed by non-uniform refinement (103377) again showed poor density for the RBDs and RBD/ACE2 region. B-factor blurring this initial map as above suggested two decorated RBDs. Various strategies were then trialled to locate a subset of well aligned particles. For the best strategy, the aligned ‘good’ particle set was 3D classified without alignment into eight classes. It was observed that classes showed a continuum of RBD poses in the upwards position, where the more separated the two ACE2-bearing RBDs were separated, the better resolved (with half of the classes having a better resolved RBD/ACE2-1; the other half a better resolved RBD/ACE2-2. Following class inspection, the best class in terms of ACE2/RBD resolution was then selected (41051), refined and then classified again, this time with a focussed mask around the relatively well resolved RBD/ACE2 for this particle subset, again without alignment into five classes. The class bearing the best resolved RBD/ACE2 (15,883 particles) was then locally refined focussing again at this interface, resulting in a final map with a CryoSPARC reported GSFSC resolution of 3.7 Å, bfactor - 19.2 Ų. Further refinement and classification attempts for this subset failed to improve on this. Quantification and statistical analysis Statistical analyses are reported in the results and figure legends. Neutralization was measured on pseudovirus. The percentage reduction was calculated and IC₅₀ determined using the probit program from the SPSS package. The Wilcoxon matched-pairs signed rank test was used for the analysis and two-tailed P values were calculated on geometric mean values.

Table 1. Antibodies S_{EQ ID NO. y} ⁿ _i ^{n d a} _i ^a _e ⁿ _i ⁿ o _{h n} ⁱ _h ^{di a} _i ^a _e b ^C _e ^{t C} _t ^o _{h n} C ⁱ _e ^t _h ^di _{1 2 3} ^{1 2 3 C} _t ^o H H H _L R _{L L i} ^t _n ^y _{v o} ^y _e ^l _{t o t e} ^l R R R R R a ^r _{p v} ^a _c ^{u h} _g ^r _p ^h _{g c} ^u D D D D D D A _{e e} ^{i i} C C C C C C H H _{n L L n} XBB-1 2 1 4 3 5 6 7 8 9 10 XBB-2 12 11 14 13 15 16 17 18 19 20 XBB-3 22 21 24 23 25 26 27 28 29 30 XBB-4 32 31 34 33 35 36 37 38 39 40 XBB-5 42 41 44 43 45 46 47 48 49 50 XBB-6 52 51 54 53 55 56 57 58 59 60 XBB-7 62 61 64 63 65 66 67 68 69 70 XBB-8 72 71 74 73 75 76 77 78 79 80 XBB-9 82 81 84 83 85 86 87 88 89 90 XBB- 92 91 94 93 95 96 97 98 99 100 10 Table 2. Examples of the mixed chain antibodies generated from antibodies derived from the same germline heavy chain IGHV3-53 Heavy chain (H)/light chain XBB-2H XBB-8H XBB-9H (L) of antibody XBB-2L - XBB-8H/XBB-2L XBB-9H/XBB-2L XBB-8L XBB-2H/XBB-8L - XBB-9H/XBB-8L XBB-9L XBB-2H/XBB-9L XBB-8H/XBB-9L - Table 3. Examples of the mixed chain antibodies generated from antibodies derived from the same germline heavy chain IGHV3-66 Heavy chain (H) /light XBB-3H XBB-10H chain (L) of antibody XBB-3L - XBB-10H/XBB-3L XBB-10L XBB-3H/XBB-10L - Table 4. Examples of the mixed chain antibodies generated from antibodies derived from the same germline heavy chain IGHV3-53 and 3-66 Heavy chain (H)/light XBB-2H XBB-8H XBB-9H XBB-3H XBB-10H chain (L) of antibody XBB-8H/ XBB-9H/ XBB-3H/ XBB-10H/ XBB-2L - XBB-2L XBB-2L XBB-2L XBB-2L XBB-2H/ XBB-9H/ XBB-3H/ XBB-10H/ XBB-8L - XBB-8L XBB-8L XBB-8L XBB-8L XBB-2H/ XBB-8H/ XBB-3H/ XBB-10H/ XBB-9L - XBB-9L XBB-9L XBB-9L XBB-9L XBB-2H/ XBB-8H/ XBB-9H/ XBB-10H/ XBB-3L - XBB-3L XBB-3L XBB-3L XBB-3L XBB-2H/ XBB-8H/ XBB-9H/ XBB-3H/ XBB-10L - XBB-10L XBB-10L XBB-10L XBB-10L Table 5. IC50 titres of antibodies against various psudeo-viruses IC50 ± SEM (µg/mL) of various Pseudo-viruses BQ.1.1 XBB.1. XBB.1. XBB.1. BA.2.8 BA.2 BA.4/5 BQ.1.1 + 5 5.10 5.70 6 A475V 0.004 XBB-1 0.003 ± 0.004 ± 0.018 ± 0.005 ± 0.002 ± ± >10 >10 (1-69) 0.000 0.001 0.001 0.000 0.000 0.002 0.005 XBB-2 0.003 ± 0.006 ± 0.108 ± 0.737 ± 0.013 ± 0.013 ± 0.362 ± ± (3-53) 0.000 0.000 0.007 0.029 0.002 0.005 0.134 0.001 0.006 XBB-3 0.008 ± 0.068 ± 1.568 ± 0.112 ± 0.054 ± ± >10 >10 (3-66) 0.001 0.011 0.952 0.014 0.007 0.000 0.035 XBB-4 0.008 ± 0.032 ± 0.023 ± 0.073 ± 1.795 ± 0.435 ± 0.747 ± ± (3-15) 0.001 0.005 0.001 0.001 0.193 0.026 0.036 0.001 0.200 XBB-5 0.084 ± 0.048 ± 0.418 ± 0.023 ± 0.010 ± 7.111 ± ± >10 (3-72) 0.014 0.004 0.098 0.010 0.003 1.318 0.064 0.008 XBB-6 0.008 ± 0.021 ± 0.046 ± 0.064 ± 0.124 ± ± >10 >10 (3-9) 0.002 0.007 0.016 0.007 0.030 0.001 0.133 XBB-7 0.009 ± 0.025 ± 0.106 ± 0.028 ± 0.230 ± 0.017 ± 0.025 ± ± (3-7) 0.001 0.002 0.014 0.002 0.077 0.001 0.001 0.002 0.008 XBB-8 0.008 ± 0.017 ± 0.086 ± 0.868 ± 0.011 ± 0.012 ± 0.400 ± ± (3-53) 0.001 0.000 0.015 0.106 0.001 0.005 0.015 0.001 0.006 XBB-9 0.007 ± 0.013 ± 0.004 ± 0.012 ± 0.002 ± 0.008 ± 0.004 ± ± (3-53) 0.000 0.002 0.000 0.000 0.000 0.004 0.001 0.001 XBB- 0.005 0.006 ± 0.022 ± 0.011 ± 0.028 ± 0.965 ± 10 (3- ± >10 >10 0.000 0.000 0.004 0.010 0.027 66) 0.001 Table 6. Mutations in BA.2.86 compared to BA.2 and their prevalence in previous strains Total number of Number of Mutation sequences Variants in which mutation sequences from (202-01-06 been observed BA.2.86 and to BA.2.86.1 2023-09-27) I_{ns16MPLF 141} ^{BA.2.86.1 (88.65%), BA.2.86} (_{11.35%) 141 R21T 11255} ^{AY.70 (49.06%), B.1.1.7} (_{4.02%), AY.4 (3.10%) 228} S^{50L 1286 BA.2.86.1 (17.57%), AY.4} (_{9.18%), BA.2 (4.67%)} ²⁸¹ H_{69del 6164330} ^{B.1.1.7 (18.39%), BA.1.1} (_{16.38%), BA.1 (6.95%) 298 V70del 6144727} ^{B.1.1.7 (18.36%), BA.1.1} (_{16.40%), BA.1 (6.97%) 245} V^{127F 1975 B.1.1.7 (16.05%), AY.4} (_{13.37%), BA.2.86.1 (12.05%)} ²⁹³ Y_{144del 4393871} ^{B.1.1.7 (25.22%), BA.1.1} (_{22.45%), BA.1 (9.61%) 279 F157S 20469} ^{B.1.637 (74.53%), BA.2 (5.79%),} B_{A.2.38.2 (3.19%) 287 R158G 4131634} ^{AY.4 (20.17%), AY.103 (7.24%),} A_{Y.43 (6.99%) 288 N211del 2118699} ^{BA.1.1 (41.57%), BA.1 (17.58%),} B_{A.1.17.2 (8.81%) 284 L212I 2085499} ^{BA.1.1 (41.74%), BA.1 (17.67%),} B_{A.1.17.2 (8.91%) 283 L216F 11355} ^{AY.4 (21.34%), B.1.1.7} (_{17.54%), AY.43 (4.01%) 289 H245N 13638} ^{BA.2.3.20 (35.62%), CM.8.1} (_{8.74%), CM.2 (8.64%) 288} A264D 442 ^{BA.2.86.1 (51.36%), BA.2.86} (_{11.99%), BN.1.3.13 (7.69%)} 280 I_{332V 405} ^{BA.2.86.1 (57.78%), BA.2.86} (_{13.33%), B.1.1.7 (8.64%) 208 G339H 874448} ^{XBB.1.5 (20.99%), XBB.1.16} (_{3.39%), CH.1.1 (2.46%) 287} ^{K356T 83047 BN.1.3 (21.40%), BN.1.2} (_{11.64%), BN.1 (7.74%)} ²⁷⁸ _{R403K 3739} ^{EG.10.1 (12.36%), XBB.1.41.1} (_{10.27%), EG.7 (6.82%) 217 V445H 298} ^{BA.2.86.1 (74.16%), BA.2.86} (_{11.41%), XBB.1.5 (2.68%) 255 G446S 2645291} ^{BA.1.1 (30.19%), BA.1 (11.07%),} X_{BB.1.5 (6.71%) 258} ^{N450D 35714 BF.14 (22.28%), BA.2.3.20} (_{13.41%), BA.5.5.1 (8.84%)} ²⁵⁵ _{L452W 457} ^{BA.2.86.1 (47.92%), AY.103} (_{6.56%), BA.2.86 (6.56%) 249 N460K 1346078} ^{XBB.1.5 (13.32%), BQ.1.1} (_{11.99%), BQ.1 (3.65%) 261 N481K 2276} ^{BA.2.86.1 (9.80%), B.1 (8.17%),} B_{N.1.5.2 (7.73%) 251 V483del 2897} ^{BA.2 (30.69%), BA.1.1 (11.53%),} B_{.1.1.7 (8.01%) 215 E484K 265560} ^{P.1 (29.34%), B.1.351 (12.34%),} B_{.1.526 (9.40%) 241} F486P 640415 ^{XBB.1.5 (28.42%), XBB.1.16} (_{4.37%), XBB.1.9.1 (2.66%)} 271 Q493R _reversion ³⁹⁷²⁸³ XBB.1.5 (12.90%), XBB.1.16 (_{6.52%), EG.5.1.1 (4.29%)} ²⁸⁰ _{E554K 6336} ^{FL.10.1 (26.03%), XBB.1.19.1} (_{9.44%), FL.25 (6.17%) 290} ^{A570V 2660 B.1.2 (16.95%), BA.2.86.1} (_{8.91%), BA.5.1.24 (4.66%)} ^{291 P621S 8669 XBB.1.5.91 (8.93%), XBB.1.5.50} (_{7.23%), XBB.1.5.90 (4.42%)} ²⁸⁸ _{I670V 4700} ^{BA.4.1.1 (63.64%), B.1.1.7} (_{4.51%), AY.4 (2.66%) 2 P681R 4488343} ^{AY.4 (19.61%), B.1.617.2} (_{7.19%), AY.103 (7.16%) 289} ^{S939F 30916 B.1.619.1 (10.29%), AY.4} (_{7.57%), B.1.1.7 (7.51%)} ²⁸⁶ _{P1143L 4629} ^{BA.2 (27.65%), BA.2.86.1} (_{5.14%), BQ.1.1 (4.67%) 293} Table 7. V^{3+18M V4+6M} BA.2 BA.4/5 Latest Infection Infection Infection Participants F_{emale 12 16 16 6 16} Male 5 7 3 5 2 Median age 36 (Range 43 (Range 45 (Range 42 (Range

H_istory First dose P^{fizer/BioNtech 13 17 16 8} O_{xford/AstraZeneca 3 6 3 2 Moderna 1 0} Second dose P^{fizer/BioNtech 13 17 16 8} O_{xford/AstraZeneca 3 6 3 2 Moderna 1 0} Third dose P^{fizer/BioNtech 16 23 18 4} M_{oderna 1 0 1 4} Fourth dose Pfizer/BioNtech (Bivalent)

P_{fizer/BioNtech 1 Moderna (Bivalent) 5} Fifth dose

H_istory I^{nfected 12 20 19 11 19} Naïve 5 3 0 0 0 Table 8. Variant infected ^{Date swab} c_ollected 1 BE.1_OMICRON 21/12/2022 2 CH.1.1.2_OMICRON 3 CH.1.1_OMICRON 31/01/2023 4 BQ.1.1_OMICRON 04/01/2023 5 19/01/2023 6 21/12/2022 7 06/01/2023 8 BA.5.2-10 9 BA.5.2-11 10 BA.5.2-12 11 BA.5.2-13 12 BA.5.2-14 13 24/01/2023 14 17/01/2023 15 17/01/2023 16 BE.1_OMICRON 14/08/2022 17 BA.2.73_OMICRON 16/09/2022 18 BA.5.1_OMICRON 09/10/2022 19 XBB.1.5_OMICRON 26/02/2023 Table 9. Ig variable gene usage for XBB mAbs Heavy chain Light chain ^{Ab id. Protein-} Number V- D- L Number J-GENE S_pecific of AA ight G_ENE ^J-GENE GENE Chain of AA V-GENE and allele and changes changes allele _{XBB-1 RBD 14} ^1-69*01 F _{2*01 F} 3-22*01 F ^{k 11 4-1*01 F 1*01 F 3-53*} 5-12*01 1-33*01, _{XBB-2 RBD 11} ⁰¹ F _{4*02 F F} ^{k 7} or 1D- 2*01 F 33*01 F _{XBB-3 RBD 14} ^3-66*01 2-15*01 F _{6*02 F F} ^{k 6 1-9*01 F 5*01 F} 3- 1- _{XBB-4 RBD 7} ^3-15*07 F _{4*02 F} 3*01 F ^{k 5} 39*01,1D- 4*01 F 39*01 F 6 1-39*01 _{XBB-5 RBD 11} ^3-72*01 *01 F, 4-17*01 F or 6*02 F _F ^{k 13} F, or1D- 4*01 F 39*01 F _{XBB-6 RBD 8} ^3-9*01 _{6*02 F} 6-19*01 F _F ^{λ 9 2-14*01 F 1*01 F} _{XBB-7 RBD 12} ^3-7*01 _{6*02 F} 3-22*01 ^{λ 8 2-14} 2*01 F, F _F ^{*03 F} or 3*01 F 3^-5 1-1*01 1-33*01 _{XBB-8 RBD 9} ^3*01 F _{6*02 F F} ^{k 6} F, or 1D- 5*01 F 33*01 F 6*02 F or 1-2 1-33*01 _{XBB-9 RBD 19} ^3-53*02 6*01 F 1*01 F, F 4*03 _F ^{k 13} , or 1D- 33*01 F or 3*01 F XBB- 3-66*01 3-10*01 1-33*01 ₁₀ ^{RBD 11} _F ^{4*02 F} _F ^{k 8} F, or 1D- 2*04 F 33*01 F Table 10. Data collection, structure determination and refinement statistics

Sequence Listing Amino acid and nucleotide sequences of heavy chain and light chain variable regions of antibodies Heavy chain Antibo SEQ SEQ dy Nt sequence ID AA sequence ID NO: NO: gaggtgcagctgttggagtctggggctgaggtgaa gaagtctgggtcctcggtgagggtctcctgcaaggc EVQLLESGAEVKK ttctggaggctcatttagcagggatgctatcagctgg SGSSVRVSCKASG gtgcgacaggcccctggacaagggcttgagtggat GSFSRDAISWVRQ gggagggatcatccctatttttgctacaccacactac APGQGLEWMGGII XBB-1 gcacagaagttccaggacagagtcacgattaccgc 1 PIFATPHYAQKFQD gacgaatccacgagcacggcccacatggaattga RVTITA 2 g DESTSTAH gcagcctgagatctgaggacacggccctgtattact MELSSLRSEDTALY gtgcgagagccacaagtgtcgatagtgatggtctttt YCARATSVDSDGL gcccgccaacctcgactggtacttcgatctctgggg LPANLDWYFDLW ccgtggcaccctggtcaccgtctcctcag GRGTLVTVSS gaggtgcagctggtggagtctggaggaggcttagtc gagccgggggggtccctgcgactctcctgtgcagc EVQLVESGGGLVE ctctgggatcaccgtcagtagcaactacatgcactgg PGGSLRLSCAASGI gtccgccaggctccagggagggggctggagtggg TVSSNYMHWVRQ tctcacttatttatagcggtggtagtacattcttcgcag APGRGLEWVSLIYS XBB-2 agtccgtgaagggccgattcaccatctccagagaca 11 GGSTFFAESVKGRF 12 attccaagaatacgatgtatcttcaaatgaacagcctg TISRDNSKNTMYL agagtcgaggacacggccgtctactattgtgcgaga QMNSLRVEDTAVY gaggtgccccgaattagtggctacgattactggggc YCAREVPRISGYDY cagggaaccctggtcaccgtctcctcag WGQGTLVTVSS gaggtgcagctggtggagtctgggggaggcttggt ccagccgggggggtccctgagactctcctgtgcag EVQLVESGGGLVQ cctctgaaatcctcgtcaataggaattacatgacgtg PGGSLRLSCAASEI ggtccgccaggctccagggaaggggctggagtgg LVNRNYMTWVRQ gtctcagtcatcta APGKGLEWVSVIY XBB-3 tgccggtggtactacacactacg cggactccgtgaagggcagattcatcatctccagag 21 AGGTTHYADSVKG 22 acgattccaagaacacgttgtatcttcaaatgaatagt RFIISRDDSKNTLYL gtgacagccgaggacacggctgtgtatttctgtgcg QMNSVTAEDTAVY agagatctagtggtccacggtatggacgtctggggc FCARDLVVHGMD caagggatcacggtcaccgtctcttcag VWGQGITVTVSS gaggtgcagctggtgcagtctgggggaggcctggt aaagcctggggggtcccttagactctcctgtgcagc EVQLVQSGGGLVK ctctggtttctctttcactaacgcctggatgaactgggt PGGSLRLSCAASGF ccgccaggctccagggaagggactggagtgggtc SFTNAWMNWVRQ XBB-4 ggccgcattaaaagcaaagctgatggtgggacaac 31 APGKGLEWVGRIK SKADGGTTD 32 agactacgctgcacccgtgaaaggcaaattcaccat YAAP ctcaagagatgattcaaaaaacacgctgtatctgcaa VKGKFTISRDDSKN atgaatagcctgaaaaccgaggacacagccatttatt TLYLQMNSLKTED actgtacctcagatgtttacgatttttcgactggttttgg TAIYYCTSDVYDFS gcaacgcgacgattttgactactggggccagggaa TGFGQRDDFDYWG ccctggtcaccgtctcctcag QGTLVTVSS caggtgcagctggtggagtctggggggggcttggt ccagcctggagggtccctgagactctcctgtgcagc QVQLVESGGGLVQ ctctggattcgccttcagtgaccactacatggactgg PGGSLRLSCAASGF gtccgccaggctccagggaaggggctggagtggg AFSDHYMDWVRQ ttggccgtattagcaataaaggtaacaattacatcaca APGKGLEWVGRIS XBB-5 caatacgccgcgtctgtgaaaggcagattcaccatct 41 NKGNNYITQYAAS VKGRFTI 42 caagagatgattcaaagaacttactatatctgcaagtg SRDDSKN aacagcctgcaaaccgaggacacggccgtgtattat LLYLQVNSLQTED tgtgctagagacttcctgtacggtccctactacggttt TAVYYCARDFLYG ggacgtctggggtcaggggaccacggtcaccgtct PYYGLDVWGQGTT cctcag VTVSS gaggtgcagctgttggagtctgggggaggcttggta cagcctggcaggtccctgagactctcctgtgcagcc EVQLLESGGGLVQ tctggattcacctttgatgattatgccatacactgggtc PGRSLRLSCAASGF cggcaagttccagggaagggcctggagtgggtctc TFDDYAIHWVRQV aggtattagttggaatagtgacaccatagactatgcg PGKGLEWVSGISW XBB-6 gactctgtgaagggccgattcaccatctccagagac 51 NSDTIDYADSVKG tgtatctgcaaatgaacagt RFTISRDNAEN 52 aacgccgagaactccc SLY ctgagaggtgaggacacggccttgtattactgtgcaa LQMNSLRGEDTAL aatcttcattccccggatatagcagtggctggtactac YYCAKSSFPGYSSG ggtttggacgtgtggggccaagggaccacggtcac WYYGLDVWGQGT cgtctcctcag TVTVSS caggtgcagctggtggagtctgggggaggcttggt ccagcctggggggtccctgagactctcctgtgcagc QVQLVESGGGLVQ ctctggatttatctttagaagcttttcgatgagctgggt PGGSLRLSCAASGF ccgccaggctccagggaaggggctggagtgggtg IFRSFSMSWVRQAP gccaacataaacgaagatggaggtgagaaatactat GKGLEWVANINED XBB-7 gtggactctgtgaagggccgattcaccatctccaga 61 GGEKYYVDSVKGR ca FTISRDYAKDS 62 gactacgccaaggactcagtgtttctgcaaatgaa VFL gcctgagagccgaggacacggctgtgtattactgtg QMNSLRAEDTAVY cgagagtgggaccctattattatgatagtgctggttatt YCARVGPYYYDSA accgacgccactaccacttcggtatggacgtctggg GYYRRHYHFGMD gccaagggaccacggtcaccgtctcctcag VWGQGTTVTVSS caggtgcagctggtggagtctggaggaggcttgatc cagcctggggggtctctgagaatctcttgtgcagcct QVQLVESGGGLIQP ctgagatcaccgtcagcagcaactacatgaactggg GGSLRISCAASEITV tccgccaggctccagggaaggggctggagtgggtc SSNYMNWVRQAP tcagttctttacagtggtggaacc GKGLEWVSVLYSG XBB-8 acatactacgcag acgccgtgaagggccgattcaccatctccagagac 71 GTTYYADAVKGRF 72 aattccaagaacacgctgtatcttcaaatgaacagtct TISRDNSKNTLYLQ gagagtcgaggacacggccgtttattattgtgcgag MNSLRVEDTAVYY agatctgggtccggctgggggtatggacgtctggg CARDLGPAGGMD gccaagggaccacggtcaccgtctcctcag VWGQGTTVTVSS caggtgcagctggtggagactggaggaggcttggt QVQLVETGGGLVQ ccagccgggggggtccctaagactctcctgtgaag PGGSLRLSCEASEII XBB-9 cctctgagataatcgtcagtgccaactacatgacctg ggtccgccaggctccagggaaggggctggagtgg 81 VSANYMTWVRQA PGKGLEWVSLIYPG 82 gtctcacttatttatcccggtggcaccacatacctctca GTTYLSDSLKGRFT gactccctgaagggccgattcaccgtctccagagac VSRDNSKNTMNLE aactccaagaatacgatgaatcttgaaatgaacagcc MNSLRAGDTAVYY tgagagccggggacacggccgtctattactgtgcga CARLIVGGIAGMD ggttaatagtgggaggaatagccggcatggacgtct VWGQGTTVTVSS ggggccaagggaccacggtcaccgtctcctcag caggtgcagctggtggagtctgggggaggcttggt ccagcctggggggtctctgagactctcctgtgcagc QVQLVESGGGLVQ ctctgaaattatcgtcgataggaactacatgagttggg PGGSLRLSCAASEII tccgccaggctccagggaaggggctggagtgggtc VDRNYMSWVRQA XBB- tcacttatttatgccggcggcagtacattctacgcaga PGKGLEWVSLIYA 10 ctccgtgaagggcagattcaccatctccagagacac 91 GGSTFYADSVKGR 92 tgtcaagaacacactttatcttcaaatgaacagcctga FTISRDTVKNTLYL gagccgaagacacggctgtgtattactgtgcgagag QMNSLRAEDTAVY ggcgatatttgacatatgactcctggggccagggaa YCARGRYLTYDSW ccctggtcaccgtctcctcag GQGTLVTVSS Light chain Antibo SEQ SEQ dy Nt sequence ID AA sequence ID NO: NO: gccatccggatgacccagtctccagactccctggct gtgtctctgggcgagagggccacgatcaactgcaa AIRMTQSPDSLAVS gtccagccagagtgttttaaaccgctccagcaacaa LGERATINCKSSQS gaacttcttagcttggtaccagcagaaaccacgaca VLNRSSNKNFLAW gcctcctaaactcctcattt YQQKPRQPPKLLIY XBB-1 actgggcatctacccgga aatccggggtccctgaccgattcagtggcagcgggt 3 WASTRKSGVPDRF 4 ctgggacagatttcactctcaccatcaacagcctgca SGSGSGTDFTLTIN ggctgaagatgtggcagtttattcctgtcagcaatatt SLQAEDVAVYSCQ atagttctccgacgttcggccaagggaccaaggtgg QYYSSPTFGQGTK agattaaac VEIK gacatccagatgacccagtctccatcctccctgtctg cgtctgtaggagacagagtcaccatcacttgccagg DIQMTQSPSSLSAS ccagtcaggacattaataagtatttaaattggtatcag VGDRVTITCQASQ cagaaaccagggaaagcccctaacctcctgatctcc DINKYLNWYQQKP XBB-2 ggtgcatccaatttggaaacaggggtcccatcaagg 13 GKAPNLLISGASNL tcagtggaagtggatttgggacagattttaccttcac ETGVPS 14 t RFSGSGFG catcagcagcctgcagcctgaagatattgcaacatat TDFTFTISSLQPEDI tactgtcaacagtctgataatctccctcccacttttggc ATYYCQQSDNLPP caggggaccaaagtggaaatcaaac TFGQGTKVEIK gacatccagttgacccagtctccatccttcctgtctgc atctataggcgacagagtcaccatcacttgccgggc DIQLTQSPSFLSASI cagtcagggcattagcaataatttaggttggtatcagc GDRVTITCRASQGI agaaaccagggaaagcccctaagctcctgatctatg SNNLGWYQQKPG XBB-3 ctgcatccactttgcaaagtggcgtcccatcaaggtt 23 KAPKLLIYAASTLQ SGVP 24 cagcggcagtggatctgggacagaattcactctcac SRFSGSGSGT aatcagcagcctgcagcctgaagattttgcaacttatt EFTLTISSLQPEDFA actgtcaagagcttaatgattacccgaccttcggcca TYYCQELNDYPTF agggacacgactggagattaaac GQGTRLEIK gacatcgtgatgacccagtctccatcctccctgtctgc DIVMTQSPSSLSAS XBB-4 atctgtaggagacagagtcaccatcacttgccgggc 33 VGDRVTITCRASQS 34 aagtcagagcattagctactttttaaattggtatcagca ISYFLNWYQQKPG gaaaccagggaaagcccctaagctcctgatctctgc KAPKLLISAASSLQ tgcatccagtttgcagagtggggtcccatcaaggttc SGVPSRFSGSGSGT agtggcagtggatctgggacagatttcactctcacca DFTLTISSLQPEDFA tcagtagtctgcaacctgaagattttgcaacttactact TYYCQQSYSSLITF gtcaacagagttacagttccctgatcactttcggcgg GGGTKVEIK agggaccaaggtggaaatcaaac gccatccagatgacccagtctccatcctccctgtctg catctgtaggagacagagtcaccatcacttgccggg AIQMTQSPSSLSAS caagtcagagcattagcagctatttaaattggtatcag VGDRVTITCRASQS cagaaagcagggagagcccctacactcctgatctct ISSYLNWYQQKAG XBB-5 gatgcatccaggttgcgaagtggggtcccatcaagg 43 RAPTLLISDASRLR cagtggatctgagacagatttcactctcac SG 44 ttcagtgg VPSRFSGSGSET catcaacagtctgcaacctgaagattttgcaacttact DFTLTINSLQPEDF actgtcaacagacttccagtagtcccccccccactttc ATYYCQQTSSSPPP ggcggagggaccaaagtggatatcaaac TFGGGTKVDIK cagactgtggtgacccagcctgcctccgtgtctgggt ctcctggacagtcgatcaccatctcttgcactggaac QTVVTQPASVSGSP cagcagtgacgttggtggttataactatgtctcctggt GQSITISCTGTSSDV accaacagtacccaggcaaagcccccaaagtcatc GGYNYVSWYQQY XBB-6 atttttgaggtcggtaatcggccctcaggggtttctaat 53 PGKAPKVIIFEVGN ggcctccc RPSG 54 cgcttctctggctccaagtctggcaacac VSNRFSGSKS tgaccatctctgggctccaggctgaggacgaggctg GNTASLTISGLQAE attattattgcagctcatatacaagcaccagcactgga DEADYYCSSYTSTS gtcttcggaactgggaccaaggtcaccgtcctag TGVFGTGTKVTVL cagtctgccctgactcagcctgcctccgtgtctgggt QSALTQPASVSGSP ctcctggacagtcgatcaccatctcctgcactggaac GQSITISCTGTSSDI cagcagtgacattggtgattataactatgtctcctggt GDYNYVSWYQQH accaacaacacccaggcaaagcccccaaactcatg PGKAPKLMILYVT XBB-7 attctttatgtcactgatcggccctcaggggtttctaat 63 DRPSGVSNRFSGSK 64 cgcttctctggctccaagtctggcaacacggcctccc SGNTASLTISGLQA tgaccatctctgggctccaggctgaggacgaggctg EDEADYYCSSYTG attattattgtagctcatacacaggcagtgtcacggtat SVTVFGGGTKLTV tcggcggagggaccaagctgaccgtcctgg L gccatccagatgacccagtctccatcctccctgtctg catctgtaggagacagagtcaccatcacttgccagg AIQMTQSPSSLSAS cgagtcaggacattaataaatatttaaattggtatcag VGDRVTITCQASQ cagagaccaggtaaagcccctaagctcctgatctac DINKYLNWYQQRP XBB-8 gatgcatccaatttgaaaacgggggtcccatcgagg 73 GKAPKLLIYDASNL KTGVPSR 74 ttcagtggaagtggatctgggacagattttactttcac FSGSGSG catcagcagcctgcagcctgaagatattgcgacatat TDFTFTISSLQPEDI tactgtcatcagtatgataatctccctccaaccttcggc ATYYCHQYDNLPP caagggacacgactggagattaaac TFGQGTRLEIK gccatccagttgacccagtctccatcctccctgtctgc atctgtaggagacagagtcaccatcacttgccaggc AIQLTQSPSSLSASV gactcacgacattaacaagtttttaaattggtatcagc GDRVTITCQATHDI aaaaaccagggaaagcccctaagctcctgatctacg NKFLNWYQQKPG XBB-9 atgcttccaatttggaaacaggggtcccatcaagatt 83 KAPKLLIYDASNLE acaacttttactttcacca TGVPSRFSGSGFG 84 cagtggaagtggctttggg T tcagcagcctgcagcctgaagatattgcaacatactt TFTFTISSLQPEDIA ctgtcatcaatatgaaaatatccctccgattttcggccc TYFCHQYENIPPIFG tgggaccaaggtggaaatcaaac PGTKVEIK gaaatagtgatgacgcagtctccatcctccctgtctg catctgtaggagacagagtcaccatcacttgccggg EIVMTQSPSSLSAS cgagtcaagacattaacaagtctttaaattggtatcag VGDRVTITCRASQ cagaaaccaggaaaag DINKSLNWYQQKP XBB- ccccaaagctcctgatcta cgat GKAPKLLIYDASNL 10 gcatccaatttggaaacaggggtcccatcaag 93 ETGV 94 gttcagtggaagtggatctgggacagattttactttca PSRFSGSGSG ccatcagcagcctgcagcccgaagatattgcaacat TDFTFTISSLQPEDI attactgtcaacagtatgatagtatccctccgtgcagtt ATYYCQQYDSIPPC ttggccaggggaccaaagtggatatcaaac SFGQGTKVDIK CDR sequences of antibodies H_{eavy chain CDR} SE Ab SEQ SEQ Q n_umber ^CDR1-IMGT ID CDR2-IMGT ID CDR3-IMGT ID NO. NO. NO . X_{BB-1 GGSFSRDA 5 IIPIFATP 6} ^{ARATSVDSDGLLP} A_{NLDWYFDL 7} XBB-2 GITVSSNY 15 IYSGGST 16 AREVPRISGYDY 17 XBB-3 EILVNRNY 25 IYAGGTT 26 ARDLVVHGMDV 27 X_{BB-4 GFSFTNAW 35 IKSKADGGTT 36} ^{TSDVYDFSTGFGQ} R_{DDFDY 37 XBB-5 GFAFSDHY 45 ISNKGNNYIT 46} ^{ARDFLYGPYYGLD} V _{47 XBB-6 GFTFDDYA 55 ISWNSDTI 56} ^{AKSSFPGYSSGWY} Y_{GLDV 57 XBB-7 GFIFRSFS 65 INEDGGEK 66} ^{ARVGPYYYDSAGY} Y_{RRHYHFGMDV 67} XBB-8 EITVSSNY 75 LYSGGTT 76 ARDLGPAGGMDV 77 XBB-9 EIIVSANY 85 IYPGGTT 86 ARLIVGGIAGMDV 87 XBB- 1₀ ^{EIIVDRNY 95 IYAGGST 96 ARGRYLTYDS 97} Light Chain CDR SEQ SEQ SEQ Antibody CDR1-IMGT ID CDR2-IMGT ID CDR3-IMGT ID NO. NO. NO. XBB-1 QSVLNRSSNKNF 8 WAS 9 QQYYSSPT 10 XBB-2 QDINKY 18 GAS 19 QQSDNLPPT 20 XBB-3 QGISNN 28 AAS 29 QELNDYPT 30 XBB-4 QSISYF 38 AAS 39 QQSYSSLIT 40 XBB-5 QSISSY 48 DAS 49 QQTSSSPPPT 50 XBB-6 SSDVGGYNY 58 EVG 59 SSYTSTSTGV 60 XBB-7 SSDIGDYNY 68 YVT 69 SSYTGSVTV 70 XBB-8 QDINKY 78 DAS 79 HQYDNLPPT 80 XBB-9 HDINKF 88 DAS 89 HQYENIPPI 90 XBB-10 QDINKS 98 DAS 99 QQYDSIPPCS 100 SEQ ID NO: 101 - Germline IGHV3-53 v-region sequence, with the CDR1-3 in bold and underlined: EVQLVETGGGLIQPGGSLRLSCAASGFTVSSNYMSWVRQAPGKGLEWVSVIYSG GSTYYADSVKGRFTISRDNSKNTLYLQMNSLRAEDTAVYYCARGIVGATYYYYY GMDVWGQGTTVTVSS SEQ ID NO: 102 - Germline IGκV1-33 v-region sequence, with the CDR1-3 in bold and underlined: DIQMTQSPSSLSASVGDRVTITCQASQDISNYLNWYQQKPGKAPKLLIYDASNLET GVPSRFSGSGSGTDFTFTISSLQPEDIATYYCQQYDNLPWTFGQGTKVEIK SEQ ID NO: 103 – Spike Glycoprotein amino acid sequence of WIV04 isolate Genbank Ref. QHR63260.2: MFVFLVLLPLVSSQCVNLTTRTQLPPAYTNSFTRGVYYPDKVFRSSVLHSTQDLFL PFFSNVTWFHAIHVSGTNGTKRFDNPVLPFNDGVYFASTEKSNIIRGWIFGTTLDSK TQSLLIVNNATNVVIKVCEFQFCNDPFLGVYYHKNNKSWMESEFRVYSSANNCTF EYVSQPFLMDLEGKQGNFKNLREFVFKNIDGYFKIYSKHTPINLVRDLPQGFSALE PLVDLPIGINITRFQTLLALHRSYLTPGDSSSGWTAGAAAYYVGYLQPRTFLLKYN ENGTITDAVDCALDPLSETKCTLKSFTVEKGIYQTSNFRVQPTESIVRFPNITNLCPF GEVFNATRFASVYAWNRKRISNCVADYSVLYNSASFSTFKCYGVSPTKLNDLCFT NVYADSFVIRGDEVRQIAPGQTGKIADYNYKLPDDFTGCVIAWNSNNLDSKVGGN YNYLYRLFRKSNLKPFERDISTEIYQAGSTPCNGVEGFNCYFPLQSYGFQPTNGVG YQPYRVVVLSFELLHAPATVCGPKKSTNLVKNKCVNFNFNGLTGTGVLTESNKKF LPFQQFGRDIADTTDAVRDPQTLEILDITPCSFGGVSVITPGTNTSNQVAVLYQDVN CTEVPVAIHADQLTPTWRVYSTGSNVFQTRAGCLIGAEHVNNSYECDIPIGAGICA SYQTQTNSPRRARSVASQSIIAYTMSLGAENSVAYSNNSIAIPTNFTISVTTEILPVS MTKTSVDCTMYICGDSTECSNLLLQYGSFCTQLNRALTGIAVEQDKNTQEVFAQV KQIYKTPPIKDFGGFNFSQILPDPSKPSKRSFIEDLLFNKVTLADAGFIKQYGDCLGD IAARDLICAQKFNGLTVLPPLLTDEMIAQYTSALLAGTITSGWTFGAGAALQIPFA MQMAYRFNGIGVTQNVLYENQKLIANQFNSAIGKIQDSLSSTASALGKLQDVVNQ NAQALNTLVKQLSSNFGAISSVLNDILSRLDKVEAEVQIDRLITGRLQSLQTYVTQQ LIRAAEIRASANLAATKMSECVLGQSKRVDFCGKGYHLMSFPQSAPHGVVFLHVT YVPAQEKNFTTAPAICHDGKAHFPREGVFVSNGTHWFVTQRNFYEPQIITTDNTFV SGNCDVVIGIVNNTVYDPLQPELDSFKEELDKYFKNHTSPDVDLGDISGINASVVNI QKEIDRLNEVAKNLNESLIDLQELGKYEQYIKWPWYIWLGFIAGLIAIVMVTIMLC CMTSCCSCLKGCCSCGSCCKFDEDDSEPVLKGVKLHYT ķĹ

Claims

Claims 1. An antibody capable of binding to the spike protein of coronavirus SARS-CoV-2, wherein the antibody comprises the six CDRs of antibody XBB-9, or of any one of the antibodies in Tables 1 to 4.

2. The antibody according to claim 1, comprising a heavy chain variable domain and a light chain variable domain comprising or consisting of an amino acid sequence having at least 80% identity to the heavy chain variable domain and light chain variable domain, respectively, of an antibody in any one of Tables 1 to 4.

3. The antibody according to any one of the preceding claims, wherein the antibody: (a) comprises the six CDRs of antibody XBB-9, which are CDRH1, CDRH2, CDRH3, CDRL1, CDRL2 and CDRL3 having the amino acid sequences specified in SEQ ID NOs: 85, 86, 87, 88, 89 and 90, respectively, optionally wherein the antibody comprises a heavy chain variable domain and a light chain variable domain having at least 80% identity to the amino acid sequences specified in SEQ ID NOs: 82 and 84, respectively; (b) comprises the six CDRs of antibody XBB-1, which are CDRH1, CDRH2, CDRH3, CDRL1, CDRL2 and CDRL3 having the amino acid sequences specified in SEQ ID NOs: 5, 6, 7, 8, 9 and 10, respectively, optionally wherein the antibody comprises a heavy chain variable domain and a light chain variable domain having at least 80% identity to the amino acid sequences specified in SEQ ID NOs: 2 and 4, respectively; (c) comprises the six CDRs of antibody XBB-2, which are CDRH1, CDRH2, CDRH3, CDRL1, CDRL2 and CDRL3 having the amino acid sequences specified in SEQ ID NOs: 15, 16, 17, 18, 19 and 20, respectively, optionally wherein the antibody comprises a heavy chain variable domain and a light chain variable domain having at least 80% identity to the amino acid sequences specified in SEQ ID NOs: 12 and 14, respectively; (d) comprises the six CDRs of antibody XBB-3, which are CDRH1, CDRH2, CDRH3, CDRL1, CDRL2 and CDRL3 having the amino acid sequences specified in SEQ ID NOs: 25, 26, 27, 28, 29 and 30, respectively, optionally wherein the antibody comprises a heavy chain variable domain and a light chain variable domain having at least 80% identity to the amino acid sequences specified in SEQ ID NOs: 22 and 24, respectively; (e) comprises the six CDRs of antibody XBB-4, which are CDRH1, CDRH2, CDRH3, CDRL1, CDRL2 and CDRL3 having the amino acid sequences specified in SEQ ID NOs: 35, 36, 37, 38, 39 and 40, respectively, optionally wherein the antibody comprises a heavy chain variable domain and a light chain variable domain having at least 80% identity to the amino acid sequences specified in SEQ ID NOs: 32 and 34, respectively; (f) comprises the six CDRs of antibody XBB-5, which are CDRH1, CDRH2, CDRH3, CDRL1, CDRL2 and CDRL3 having the amino acid sequences specified in SEQ ID NOs: 45, 46, 47, 48, 49 and 50, respectively, optionally wherein the antibody comprises a heavy chain variable domain and a light chain variable domain having at least 80% identity to the amino acid sequences specified in SEQ ID NOs: 42 and 44, respectively; (g) comprises the six CDRs of antibody XBB-6, which are CDRH1, CDRH2, CDRH3, CDRL1, CDRL2 and CDRL3 having the amino acid sequences specified in SEQ ID NOs: 55, 56, 57, 58, 59 and 60, respectively, optionally wherein the antibody comprises a heavy chain variable domain and a light chain variable domain having at least 80% identity to the amino acid sequences specified in SEQ ID NOs: 52 and 54, respectively; (h) comprises the six CDRs of antibody XBB-7, which are CDRH1, CDRH2, CDRH3, CDRL1, CDRL2 and CDRL3 having the amino acid sequences specified in SEQ ID NOs: 65, 66, 67, 68, 69 and 70, respectively, optionally wherein the antibody comprises a heavy chain variable domain and a light chain variable domain having at least 80% identity to the amino acid sequences specified in SEQ ID NOs: 62 and 64, respectively; (i) comprises the six CDRs of antibody XBB-8, which are CDRH1, CDRH2, CDRH3, CDRL1, CDRL2 and CDRL3 having the amino acid sequences specified in SEQ ID NOs: 75, 76, 77, 78, 79 and 80, respectively, optionally wherein the antibody comprises a heavy chain variable domain and a light chain variable domain having at least 80% identity to the amino acid sequences specified in SEQ ID NOs: 72 and 74, respectively; or (j) comprises the six CDRs of antibody XBB-10, which are CDRH1, CDRH2, CDRH3, CDRL1, CDRL2 and CDRL3 having the amino acid sequences specified in SEQ ID NOs: 95, 96, 97, 98, 99 and 100, respectively, optionally wherein the antibody comprises a heavy chain variable domain and a light chain variable domain having at least 80% identity to the amino acid sequences specified in SEQ ID NOs: 92 and 94, respectively.

4. An antibody capable of binding to the spike protein of coronavirus SARS-CoV-2, wherein the antibody comprises CDRH1, CDRH2 and CDRH3, from a first antibody in Table 1 and CDRL1, CDRL2 and CDRL3 from a second antibody in Table 1, with the proviso that the first antibody and the second antibody are different.

5. The antibody according to claim 4, comprising a heavy chain variable domain amino acid sequence having at least 80% sequence identity to the heavy chain variable domain from a first antibody in Table 1, and a light chain variable domain amino acid sequence having at least 80% sequence identity to the light chain variable domain from a second antibody in Table 1.

6. The antibody according to claim 4 or claim 5, wherein the first and second antibodies derive from the same germline heavy chain v-region, optionally wherein the heavy chain v-region is IGHV3-53 or IGHV3-66.

7. The antibody according to any one of claims 4 to 6, wherein the first antibody and the second antibody are both selected from one of the following groups: (a) XBB-2, XBB-8, and XBB-9; optionally wherein the antibody comprises the CDRH1, CDRH2, CDRH3, CDRL1, CDRL2 and CDRL3 of one of the antibodies as set out in Table 2, optionally wherein the antibody comprises a heavy chain variable domain and a light chain variable domain having at least 80% identity to the heavy chain variable domain and a light chain variable domain, respectively, to one of the antibodies as set out in Table 2; (b) XBB-3 and XBB-10; optionally wherein the antibody comprises the CDRH1, CDRH2, CDRH3, CDRL1, CDRL2 and CDRL3 of one of the antibodies as set out in Table 3, optionally wherein the antibody comprises a heavy chain variable domain and a light chain variable domain having at least 80% identity to the heavy chain variable domain and a light chain variable domain, respectively, to one of the antibodies as set out in Table 3; or (c) XBB-2, XBB-8, XBB-9, XBB-3 and XBB-10; optionally wherein the antibody comprises the CDRH1, CDRH2, CDRH3, CDRL1, CDRL2 and CDRL3 of one of the antibodies as set out in Table 4, optionally wherein the antibody comprises a heavy chain variable domain and a light chain variable domain having at least 80% identity to the heavy chain variable domain and a light chain variable domain, respectively, to one of the antibodies as set out in Table 4.

8. The antibody according to any one of the preceding claims, which is a full-length antibody, optionally (i) comprising an IgG1 constant region, and/or (ii) comprising an Fc region comprising at least one modification such that serum half-life is extended.

9. One or more polynucleotides encoding the antibody according to any one of the preceding claims, such as a first polynucleotide encoding the heavy chain variable domain of the antibody and a second polynucleotide encoding the light chain variable domain of the antibody.

10. One or more vectors comprising the one or more polynucleotides of claim 9.

11. A host cell comprising the one or more vectors of claim 10.

12. A method for producing an antibody that is capable of binding to the spike protein of coronavirus SARS-CoV-2, the method comprising culturing the host cell of claim 11 and isolating the antibody from said culture.

13. A method of generating an antibody capable of binding to the spike protein of SARS-CoV-2, comprising raising an antibody against an epitope comprising amino acid residues at positions 455 and 456 in the spike protein of coronavirus SARS-CoV-2, relative to the spike protein of the hCoV-19/Wuhan/WIV04/2019 strain, optionally wherein the raising of the antibody is performed by hybridoma technology, phage display technology or by immunizing an animal with the modified spike protein.

14. An antibody that is: (a) obtained or obtainable by the method of claim 13; and/or (b) capable of binding to the same epitope on the spike protein as, or competes with, antibody XBB-9.

15. A pharmaceutical composition comprising: (a) one or more antibody according to any one of claims 1 to 8 and 14, and (b) at least one pharmaceutically acceptable diluent or carrier.

16. A combination of antibodies comprising two or more antibodies according to any one of claims 1 to 8 and 14.

17. The antibody according to any one of claims 1 to 8 and 14, or the pharmaceutical composition according to claim 15, for use in a method for treatment of a human or animal by therapy.

18. The antibody according to any one of claims 1 to 8 and 14, or the pharmaceutical composition according to claim 15, for use in a method of treating or preventing coronavirus infection, or a disease or complication associated with coronavirus infection.

19. A method of treating or preventing coronavirus infection, or a disease or complication associated with coronavirus infection in a subject, comprising administering a therapeutically effective amount of the antibody according to any one of claims 1 to 8 and 14, or the pharmaceutical composition according to claim 15, to said subject.

20. The method according to claim 19, wherein the method is for treating SARS-CoV- 2 infection, or a disease or complication associated therewith, such as COVID-19.

21. A method of identifying the presence of coronavirus, or a protein fragment thereof, in a sample, comprising: (i) contacting the sample with the antibody according to any one of claims 1 to 8 and 14, and (ii) detecting the presence or absence of an antibody-antigen complex, wherein the presence of the antibody-antigen complex indicates the presence of coronavirus, or a fragment thereof, in the sample.

22. A method of treating or preventing coronavirus infection, or a disease or complication associated therewith, in a subject, the method comprising identifying the presence of coronavirus according to the method of claim 21 in a sample, and treating the subject with the antibody according to any one of claims 1 to 8 and 14, an anti-viral drug or an anti-inflammatory agent.

23. Use of the antibody according to any one of claims 1 to 8 and 14, or the pharmaceutical composition according to claim 15, for preventing, treating and/or diagnosing coronavirus infection, or a disease or complication associated therewith.

24. Use of the antibody according to any one of claims 1 to 8 and 14, or the pharmaceutical composition according to claim 15, for the manufacture of a medicament for treating or preventing coronavirus infection, or a disease or complication associated therewith.

25. The antibody for use according to claim 17 or 18, the method according to any one of claims 19 to 22, or the use according to claim 23 or 24, wherein the coronavirus infection is caused by a SARS-CoV-2 strain of the lineage Victoria, alpha, beta, gamma, delta, omicron, BA.1, BA.1.1, BA.2, BA.2.10.4, BA.2.12.1, BA.2.30.2, BA.2.75, BA.2.75.2, BA.4/5, BA.4/6, BQ.1, BQ.1.1, BJ.1, BS.1, BF.7, BN.1, XBB, XBB.1, XBB.1.5, XBB.1.5.10, XBB.1.5.70, and/or BA.2.86.