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WO2024115785A1 - Vaccin - Google Patents

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Publication number
WO2024115785A1
WO2024115785A1 PCT/EP2023/084025 EP2023084025W WO2024115785A1 WO 2024115785 A1 WO2024115785 A1 WO 2024115785A1 EP 2023084025 W EP2023084025 W EP 2023084025W WO 2024115785 A1 WO2024115785 A1 WO 2024115785A1
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WO
WIPO (PCT)
Prior art keywords
vaccine
lasv
mastomys
vector
insertion site
Prior art date
Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
Ceased
Application number
PCT/EP2023/084025
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English (en)
Inventor
Michael Jarvis
Thekla MAUCH
Wolfram Brune
Eleonore OSTERMANN
Alec REDWOOD
Baca CHAN
Andrew Davison
Jenna NICHOLS
Joseph Hughes
Matej VUCAK
Heinrich FELDMANN
Kyle ROSENKE
Frederick Hansen
Nafomon SOGOBA
Seydou DOUMBIA
Scott NUISMER
Peter Barry
Current Assignee (The listed assignees may be inaccurate. Google has not performed a legal analysis and makes no representation or warranty as to the accuracy of the list.)
Vaccine Group Ltd
Original Assignee
Vaccine Group Ltd
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Publication date
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Priority to GB2510395.3A priority Critical patent/GB2641605A/en
Publication of WO2024115785A1 publication Critical patent/WO2024115785A1/fr
Anticipated expiration legal-status Critical
Ceased legal-status Critical Current

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    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K39/00—Medicinal preparations containing antigens or antibodies
    • A61K39/12—Viral antigens
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P31/00—Antiinfectives, i.e. antibiotics, antiseptics, chemotherapeutics
    • A61P31/12—Antivirals
    • A61P31/14—Antivirals for RNA viruses
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K39/00—Medicinal preparations containing antigens or antibodies
    • A61K2039/51—Medicinal preparations containing antigens or antibodies comprising whole cells, viruses or DNA/RNA
    • A61K2039/525—Virus
    • A61K2039/5254—Virus avirulent or attenuated
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K39/00—Medicinal preparations containing antigens or antibodies
    • A61K2039/51—Medicinal preparations containing antigens or antibodies comprising whole cells, viruses or DNA/RNA
    • A61K2039/525—Virus
    • A61K2039/5256—Virus expressing foreign proteins
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K39/00—Medicinal preparations containing antigens or antibodies
    • A61K2039/55—Medicinal preparations containing antigens or antibodies characterised by the host/recipient, e.g. newborn with maternal antibodies
    • A61K2039/552—Veterinary vaccine
    • C—CHEMISTRY; METALLURGY
    • C12—BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
    • C12N—MICROORGANISMS OR ENZYMES; COMPOSITIONS THEREOF; PROPAGATING, PRESERVING, OR MAINTAINING MICROORGANISMS; MUTATION OR GENETIC ENGINEERING; CULTURE MEDIA
    • C12N2710/00—MICROORGANISMS OR ENZYMES; COMPOSITIONS THEREOF; PROPAGATING, PRESERVING, OR MAINTAINING MICROORGANISMS; MUTATION OR GENETIC ENGINEERING; CULTURE MEDIA dsDNA viruses
    • C12N2710/00011—Details
    • C12N2710/16011—Herpesviridae
    • C12N2710/16111—Cytomegalovirus, e.g. human herpesvirus 5
    • C12N2710/16141—Use of virus, viral particle or viral elements as a vector
    • C12N2710/16143—Use of virus, viral particle or viral elements as a vector viral genome or elements thereof as genetic vector
    • C—CHEMISTRY; METALLURGY
    • C12—BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
    • C12N—MICROORGANISMS OR ENZYMES; COMPOSITIONS THEREOF; PROPAGATING, PRESERVING, OR MAINTAINING MICROORGANISMS; MUTATION OR GENETIC ENGINEERING; CULTURE MEDIA
    • C12N2760/00—MICROORGANISMS OR ENZYMES; COMPOSITIONS THEREOF; PROPAGATING, PRESERVING, OR MAINTAINING MICROORGANISMS; MUTATION OR GENETIC ENGINEERING; CULTURE MEDIA ssRNA viruses negative-sense
    • C12N2760/00011—Details
    • C12N2760/10011—Arenaviridae
    • C12N2760/10034—Use of virus or viral component as vaccine, e.g. live-attenuated or inactivated virus, VLP, viral protein

Definitions

  • the present invention relates generally to a vaccine for prophylaxis or treatment of an infection by Lassa virus (LASV) or of a disorder relating to such an infection.
  • LASV Lassa virus
  • Lassa fever is an acute viral haemorrhagic illness caused by LASV which is endemic throughout much of Western Africa. Symptoms include fever, myalgia, and severe prostration, often accompanied by haemorrhagic or neurological symptoms.
  • the natural host of LASV is the Natal multimammate mouse (Mastomys natalensis), which is a species of rodent in the family Muridae that lives in large numbers in West, Central, and East Africa. It is also known as the mastomys rat, the Natal multimammate rat, the common African rat, or the African soft-furred mouse. They carry the virus in their urine and droppings and live in homes and areas where food is stored.
  • LASV has the highest human impact of any haemorrhagic fever virus. An estimated 300,000 to 500,000 Lassa fever cases are reported annually, resulting in approximately 5,000 deaths. However, the true disease burden is unknown.
  • LASV vaccine platforms currently under development have been falling short of expectations in terms of safety and efficacy. Accordingly, there remains an unmet medical need for an efficient vaccine for prophylaxis or treatment of LASV infections.
  • the inventors have developed a herpesvirus-based vaccine with a LASV transgene. Some aspects and embodiments provide or relate to a live vaccine - ideally transmissible - for vaccination of a LASV reservoir species to prevent transmission to humans.
  • the present invention is based on a series of experiments involving the cloning of two different LASV proteins into a Mastomys natalensis cytomegalovirus (mCMV) genome at two different insertion sites.
  • mCMV Mastomys natalensis cytomegalovirus
  • Figure 1 shows the geographical distribution of LASV and the virus structure.
  • LASV has a bi-segmented (L and S) single-stranded RNA genome. Each segment contains two genes in ambisense orientation.
  • the L RNA encodes a large protein, L (or RdRp) and a small zinc-binding, Z protein.
  • the S RNA encodes the major structural proteins, nucleoprotein (NP) and glycoprotein complex (GPC).
  • LASV genes utilised by the inventors are NP and GPC.
  • LASV Entry of LASV into the host cell is mediated by GPC. It is initially expressed as a single polypeptide and undergoes proteolytic cleavage to yield three subunits: glycoprotein 1 (GP1), glycoprotein 2 (GP2), and the stable signal peptide (SSP).
  • GPC glycoprotein 1
  • GP2 glycoprotein 2
  • SSP stable signal peptide
  • NP associates with L to form the ribonucleoprotein core for RNA replication and transcription and with the matrix protein Z for viral assembly.
  • Some aspects and embodiments of the present invention aim to provide a cytomegalovirusbased, self-disseminating vaccine that can be administered to a natural reservoir of LASV and spread throughout their population.
  • FIG. 2 to 4 provide an overview: MasCMV virus was isolated from Mastomys natalensis from Mali and then the Lassa virus antigen was inserted into the CMV genome to create candidate vaccines as detailed further below.
  • An aspect of the present invention provides a transmissible vaccine for LASV recombinant viralbased vaccine for Lassa fever, comprising a mastomys natalensis rat cytomegalovirus with a LASV NP gene inserted in a defined locus.
  • An aspect of the present invention provides a mastomys rat cytomegalovirus with a defined
  • LASV gene inserted in defined site in the vector virus.
  • the insertion locus may be between M25 and M25.1 ORFs.
  • the M25 and M25.1 genes most probably use the same nucleotide for polyadenylation.
  • the insertion locus may be between M78 and M79.
  • the M78 and M79 genes most probably use nucleotides for polyadenylation that are separated by three nucleotides.
  • the transgene was inserted after the first of these (AAATAACTACAATGATTGGCAAA to AAATAACTACA/ATGATTGGCAAA -> AAATAACTAC AfransgeneATGATTGGCAAA) .
  • An aspect of the present invention provides a defined MCMV (e.g. MnatCMV, MasCMV2,
  • MasCMV2a expressing a defined NP antigen fused at the N-terminus to a non-cleavable ubiquitin domain within indicated locus.
  • a further aspect provides a recombinant viral-based vaccine for Lassa fever, comprising a mastomys rat cytomegalovirus with a LASV NP gene inserted in a defined locus.
  • a further aspect provides a recombinant viral-based vector, comprising a mastomys rat cytomegalovirus (MasCMV) with a Lassa fever virus NP transgene.
  • a recombinant viral-based vector comprising a mastomys rat cytomegalovirus (MasCMV) with a Lassa fever virus NP transgene.
  • MasCMV Multiple (3) different MasCMV have been identified and isolated from Mastomys natalensis. Coinfection with multiple different MasCMVs is common.
  • MasCMV type 2 (MasCMV2) is very common in Mastomys natalensis (69% of rats).
  • MasCMV2 twelve different herpesviruses have been identified in Mastomys, but MasCMV2 is the most common. Data shows that MasCMV2 is restricted to Mastomys in the field. There is high host specificity for Mastomys supported by experimental infection studies.
  • the MasCMV may be MasCMV2.
  • the MasCMV may be MasCMV2a (a variant of MasCMV2) having GenBank accession number OP429126.1 and as described in Hasen et al. 2023. J. General Virology, Vol. 4, issue 8.
  • the MasCMV genome may be provided in the form of an infectious bacterial artificial chromosome (BAG).
  • BAG infectious bacterial artificial chromosome
  • a further aspect provides a method of making a vaccine comprising: a) propagating strains or isolates of a MnatCMV2 vector as described herein in cultured cells of a selected MnatCMV permissive cell type, thereby producing infectious MnatCMV2; and b) producing a vaccine from the propagated MasCMV.
  • the isolated viruses were sequence and only those comparable to WT viruses based on sequence were selected.
  • a further aspect provides a method of making a vaccine comprising: a) propagating strains or isolates of a MnatCMV2 vector as described herein in cultured cells of a selected MnatCMV permissive cell type, thereby producing a cell type-conditioned MnatCMV2 ; and b) producing a vaccine from the cell-type conditioned MasCMV.
  • the selected cell type may be a mastomys natalensis epithelial cell.
  • the selected cell type may be a mastomys natalensis fibroblast cell.
  • the present invention also provided cell lines for vaccine growth (either fibroblasts or epithelial).
  • the method may comprise producing a live vector vaccine, which may be transmissible. Also provides is a vaccine produced by the method described herein.
  • a vaccine composition comprising a vaccine or vector as described herein and admixed with a suitable pharmaceutical carrier or adjuvant.
  • Some aspects and embodiments provide a transmissible vaccine.
  • Disseminating vaccines formed in accordance with the present invention can be used to spread vaccine-derived immunity through a host/reservoir population as a result of their normal viral transmission. This approach limits subsequent infection of humans/domestic animals whilst simultaneously protecting the animal population involved in transmission from disease. A further goal is to decrease ability of reservoir to infect human/domestic animals.
  • the present invention may therefore include a mechanism for the production of recombinant viral vectors that express transgenes for definable periods before reversion to their benign wildtype genotype and phenotype.
  • Viral genome size is constrained by a number of factors including the capacity to efficiently package nucleic acid within the viral capsid. Viruses engineered to encode immunogenic proteins have a larger genome and are therefore at a competitive disadvantage to wild type, parental strains.
  • the LASV transgene in itself may also provide a selective pressure independent of its size towards its loss. The corollary being that antigen expression may be lost over time. However, the timing of this antigen loss is largely indeterminate.
  • the present invention provides a method for indirect inoculation of a target wildlife population comprising the steps of inoculating one or more members of a population and allowing the recombinant live virus to spread through the population.
  • the vaccine may be adapted so that the transgene has a biological “half-life” within the vaccine.
  • the present invention provides a transmissible MnatCMV-based vector with a LASV antigen.
  • the vaccine may be provided as a transmissible vaccine for use in a reservoir rodent species to prevent onward transmission to humans.
  • Nucleotide Sequence NP sequence flanked by a ubiquitin and V5 tag sequence.
  • Amino Acid Sequence NP sequence flanked by a ubiquitin and V5 tag sequence.
  • the present invention also provides a recombinant viral-based vaccine for Lassa fever, comprising a mastomys natalensis rat cytomegalovirus with a transgene comprising or consisting of a sequence as described herein or a sequence having at least 90%, 95% or 99% identity thereto.
  • the present invention also provides an immunogenic polypeptide comprising or consisting of a sequence as described herein or a sequence having at least 90%, 95% or 99% identity thereto.
  • Glycoprotein (GPC) inserted in insertion site 2
  • a non-cleavable ubiquitin may be fused to the N-terminus of LASV NP.
  • An epitope V5 tag maybe fused to the C-terminus of LASV NP.
  • LASV NP is produced with a non-cleavable ubiquitin moiety positioned at the N-terminus and a V5 epitope tag positioned at the carboxyl terminus and LASV glycoprotein (GPC) is produced without any fusions.
  • GPC LASV glycoprotein
  • Recombinant MasCMV2a LASV vectors are produced by bacterial artificial chromosome (BAC)- based construction, followed by reconstitution of BACs in MasCMV2a permissive eukaryotic cells.
  • Recombinant MasCMV2a LASV vectors could be constructed using any available methodology.
  • Protein expression is confirmed by western blot. DNA Sanger sequencing is used to confirm integrity of LASV transgene, and full genome integrity is assessed by NGS. Absence of WT MasCMV2a is demonstrated by transgene flanking specific PCR.
  • MasCMV2a LASV (and WT control) stocks are produced by reconstitution in permissive cells (either Mastomys natalensis epithelial cells or fibroblasts), with excision of the BAG cassette. Protein expression, and genome integrity are confirmed as before. Virus stocks were titred, and absence of bacterial contamination was confirmed by culture.
  • MasEFs are the fibroblasts transformed with Large T Ag, and MasKecs are the epithelial cells.
  • Figure 9a DNA electrophoresis gel, confirming correct insertion site fragments for cloning into shuttle vector, by restriction digest analysis.
  • 1 parental shuttle vector cut with EcoRI, showing expected bands at 4.8Kb & 1 .8Kb
  • Figure 9b DNA electrophoresis gel, confirming correct designated insertion site clone for cloning into shuttle vector, additional confirmation, by restriction digest analysis.
  • Figure 10a DNA electrophoresis gel, confirming correct insertion site 2 fragment in shuttle vector, by restriction digest analysis.
  • 1 parental shuttle vector cut with Nhel, Acll & BamHI, showing expected bands at 3.8Kb, 1 .4Kb, 1 .3Kb
  • 3+5 clones insertion site 9 cut with Nhel, Acll & BamHI, showing expected bands at 3.9Kb, 1 .4Kb & 1 .3Kb
  • Figure 11 b DNA electrophoresis gel, confirming correct LASV GP fragment for cloning into shuttle vector containing MasCMV2a homology domain, by restriction digest analysis.
  • Figure 12a DNA electrophoresis gel, confirming correct LASV NP fragment in shuttle vector containing MasCMV2a homology domain at insertion site 2, by restriction digest analysis.
  • 3-8 clones cut with Ncol, showing expected bands at 3.4Kb, 1 .4Kb & 1 .3Kb
  • Figure 12c DNA electrophoresis gel, confirming correct LASV GP fragment in shuttle vector containing MasCMV2a homology domain at insertion site 2, by restriction digest analysis.
  • Figure 12d DNA electrophoresis gel, confirming correct LASV GP fragment in shuttle vector containing MasCMV2a homology domain at insertion site 9, by restriction digest analysis.
  • Figure 13a DNA electrophoresis gel, confirming correct LASV NP insertion site 2 fragment for recombination into WT MasCMV2a BAG, by restriction digest analysis.
  • Figure 13b DNA electrophoresis gel, confirming correct LASV NP insertion site 9 fragment for recombination into WT MasCMV2a BAG, by restriction digest analysis.
  • Figure 13c DNA electrophoresis gel, confirming correct LASV GP insertion site 2 fragment for recombination into WT MasCMV2a BAG, by restriction digest analysis.
  • FIG. 13d DNA electrophoresis gel, confirming correct LASV GP insertion site 9 fragment for recombination into WT MasCMV2a BAG, by restriction digest analysis.
  • 1 parental shuttle vector containing insertion site 9 cut with Pmel, showing expected bands at 6.6Kb
  • Restriction enzyme analysis shows the absence of gross genomic rearrangements and the presence of predicted band shifts (marked with an *).
  • Restriction enzyme analysis shows the absence of gross genomic rearrangements and the presence of predicted band shifts (marked with an *).
  • Restriction enzyme analysis shows the absence of gross genomic rearrangements and the presence of predicted band shifts in clone P1 & P4 (marked with an *).
  • Restriction enzyme analysis shows the absence of gross genomic rearrangements and the presence of predicted band shifts in clone P1 & P9 (marked with an *).
  • Genome sequencing has been used to confirm the integrity of LASV NP insertion site 2 in these clones.
  • Clone P6 has been selected for virus stock production.
  • Genome sequencing has been used to confirm the integrity of LASV NP insertion site 9 in these clones.
  • Clone P24 has been selected for virus stock production.
  • Genome sequencing has been used to confirm the integrity of LASV GP insertion site 2 in these clones.
  • LASV GP insertion site 2 was discontinued due to the presence of genomic rearrangement in repeated BAG restriction enzyme digest and lack of virus replication.
  • Figure 15d Flanking PCR confirming correct insertion of LASV GP insertion site 9 into MasCMV2a BAG.
  • Genome sequencing has been used to confirm the integrity of LASV GP insertion site 9 in these clones.
  • LASV GP insertion site 9 was discontinued due to the presence of genomic rearrangement in repeated BAG restriction enzyme digest and lack of virus replication.
  • FIG. 16 Western blot confirming expression of MasCMV2a LASV NP insertion sites 2 + 9 virus stocks.
  • Figure 17a Flanking PCR confirming correct genome size of MasCMV2a LASV NP insertion site 2 in concentrated virus stock.
  • LASV NP insertion site 2 clone 6 (NP Ins2-P6) virus stock.
  • Nucleoprotein (NP) inserted into insertion site 2 - protein expression confirmed, virus replication comparable to WT in vivo.
  • NP nucleoprotein
  • Glycoprotein (GP) inserted in insertion site 2- no protein expression. Construct was unstable in vitro.
  • GP is not stable, regardless of insertion site.
  • Two cell lines for growth of the candidate vaccine have also been developed. More specifically a mastomys epithelial cell line (MasKECS) and fibroblast cell line (MasEFs) has been developed for vaccine growth. These are both continuous cell lines constructed by SV40 large Tag transformation.
  • Nucleoprotein (NP) inserted into insertion site 2 -> protein expression confirmed, virus replication in vivo.
  • Nucleoprotein (NP) inserted into insertion site 9 -> protein expression confirmed, virus did not replicate in vivo.
  • Glycoprotein (GP) inserted in insertion site 2 -> no protein expression.
  • Glycoprotein (GP) inserted in insertion site 9 -> no protein expression.
  • Mastomys natalensis embryonic fibroblasts were isolated from embryos (15 - 16 days of age). Briefly, embryos were trypsinized for 30-60 min, after which the connective tissue was removed by passage through a 75 pm filter and the cell pellet was collected and resuspended in DMEM containing 10% (v/v) FCS, 100 U/ml penicillin and 100 pg/ml streptomycin. Primary MasEFs at passage 1 were immortalized by retroviral transduction as described (Hinte etal., 2020, PMID 32065579).
  • the Mastomys were bred in the animal facility of the BNITM in Hamburg (https://www.bnitm.de/en/) Figure 18. Pictures showing plaques of MasCMV2a expressing LASV NP 10 days after transfection of the BAG into MasEF.
  • FIG. 19a and 19b Experimental infection studies. Initial pilot study has been performed under laboratory contained experimental conditions.
  • FIG. 20 Integrated new estimates for vaccine efficacy based on results from pilot study showing LASV viral load in salivary glands reduced by >99%. Assumes LASV load in salivary glands is proportional to transmission and efficacy is similar in Recipient animals. Indicates MasCMV2 LASV falls within critical efficacy box for effective LASV vaccine.
  • FIG. 21 Transmission study. This study was designed to determine the vaccine kinetics in Mastomys natalensis relative to shedding, vaccine replication and transmission to naive cagemates. Animals were inoculated with either CMV-LASV NP or CMV-WT at day 0 and reintroduced with their naive cage mates at day 2. Oral swabs were taken from animals (12 animals per group) at days indicated. Tissue samples from salivary glands and lung were taken after euthanasia also as indicated in the timeline.
  • FIG. 22 CMV-LASV NP vaccine shedding.
  • Viral (vaccine) shedding was determined in oral swabs by qPCR from day 0 until day 56 post-infection in directly vaccinated either (CMV-LASV NP or CMV-WT) and their co-housed animals (to assess transmission).
  • Virus copy numbers were detectable beginning from day 5 post-inoculation in all animals indicating viral shedding and transmission from vaccinated animals to their cage mates, followed by shedding from the originally naive cagemates.
  • a decrease in copy numbers starting at day 14 was observed for CMV-LASV-NP, which was delayed for CMV-WT.
  • Virus is shown to be shedding from directly inoculated animals.
  • Virus is shown to be shedding from naive animals, indicating that they must have been infected and the new virus is shedding from them.
  • FIG. 23 Vaccine replication.
  • Vaccine replication was quantified in salivary glands and lung tissue (associated with persistence and shedding) by qPCR of vaccinated and co-housed animals (CMV-LASV NP or CMV-WT) in the different animal groups (indicated based on time of euthanasia post-inoculation of directly inoculated animals).
  • Vaccine replication was detected in salivary glands at all time points tested through day 56 (last time point tested) showing longterm persistence of the vaccine in salivary glands - an established site of CMV persistence.
  • CMV-LASV NP was also detect at high levels in the lungs of all animals until day 28, and then in a subset of animals until at least day 56. The vector transmits and is released into saliva following transmission. Naive animals all have detectable virus is salivary glands and also systemically in the lungs.
  • a defined MasCMV2a expressing a defined NP antigen within an indicated locus has been investigated.
  • a vector developed in accordance with the present invention may comprise Ubiquitin fused NP codon-optimized for expression in Mas musculus under control of human CMV promoter and SV40 polyA placed within the Ins2 locus.
  • the vaccine construct (Ins2 and NP-CTL in MasCMV2) has been made, tested and animal studies demonstrate efficacy.
  • the vector expresses full-length LASV NP.
  • the vaccine is stable in culture.
  • Intrinsic control technology can confer biological half-life on CMV antigens (refer to
  • Transmissible vaccines based on cytomegalovirus is an innovative technology with the potential to provide localized population level immunity among key animal reservoir species involved in zoonotic transmission of emerging viruses.

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Abstract

L'invention concerne un vaccin recombiné à base virale contre la fièvre de Lassa, comprenant un cytomégalovirus de rat mastomys avec un gène LASV NP inséré dans un locus défini.
PCT/EP2023/084025 2022-12-02 2023-12-02 Vaccin Ceased WO2024115785A1 (fr)

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Citations (3)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
WO2008124176A2 (fr) * 2007-04-10 2008-10-16 The Administrators Of The Tulane Educational Fund Formes solubles et ancrées sur membrane de protéines de sous-unité du virus lassa
WO2019145739A1 (fr) * 2018-01-29 2019-08-01 Secretary of State for Health and Social Care Composition antigénique du virus lassa
WO2020221923A1 (fr) 2019-05-01 2020-11-05 University Of Plymouth Système intrinsèque de régulation transgénique de vecteurs viraux

Patent Citations (3)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
WO2008124176A2 (fr) * 2007-04-10 2008-10-16 The Administrators Of The Tulane Educational Fund Formes solubles et ancrées sur membrane de protéines de sous-unité du virus lassa
WO2019145739A1 (fr) * 2018-01-29 2019-08-01 Secretary of State for Health and Social Care Composition antigénique du virus lassa
WO2020221923A1 (fr) 2019-05-01 2020-11-05 University Of Plymouth Système intrinsèque de régulation transgénique de vecteurs viraux

Non-Patent Citations (6)

* Cited by examiner, † Cited by third party
Title
"GenBank", Database accession no. OP429126.1
AISLING A. MURPHY ET AL: "Self-disseminating vaccines for emerging infectious diseases", EXPERT REVIEW OF VACCINES, vol. 15, no. 1, 2 November 2015 (2015-11-02), GB, pages 31 - 39, XP055721873, ISSN: 1476-0584, DOI: 10.1586/14760584.2016.1106942 *
BRINKMANN NELE MARIE ET AL: "Understanding Host-Virus Interactions: Assessment of Innate Immune Responses in Mastomys natalensis Cells after Arenavirus Infection", VIRUSES, vol. 14, no. 9, 8 September 2022 (2022-09-08), CH, pages 1986, XP093136469, ISSN: 1999-4915, DOI: 10.3390/v14091986 *
HASEN ET AL., J.GENERAL VIROLOGY, vol. 4, 2023
KENNEDY E M ET AL: "A vaccine based on recombinant modified Vaccinia Ankara containing the nucleoprotein from Lassa virus protects against disease progression in a guinea pig model", VACCINE, ELSEVIER, AMSTERDAM, NL, vol. 37, no. 36, 19 July 2019 (2019-07-19), pages 5404 - 5413, XP085759161, ISSN: 0264-410X, [retrieved on 20190719], DOI: 10.1016/J.VACCINE.2019.07.023 *
VAN PELT F G ET AL: "Immunofluorescence studies on the association between a C-type oncornavirus and renal glomerulopathy in Praomys (Mastomys) natalensis", CLINICAL IMMUNOLOGY AND IMMUNOPATHOLOGY, SAN DIEGO, CA, US, vol. 5, no. 1, 1 January 1976 (1976-01-01), pages 105 - 118, XP026198006, ISSN: 0090-1229, [retrieved on 19760101], DOI: 10.1016/0090-1229(76)90154-9 *

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