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WO2025076039A1 - Facteur d'activité chlamydia de type protéase et compositions d'adjuvant et leurs utilisations - Google Patents

Facteur d'activité chlamydia de type protéase et compositions d'adjuvant et leurs utilisations Download PDF

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WO2025076039A1
WO2025076039A1 PCT/US2024/049528 US2024049528W WO2025076039A1 WO 2025076039 A1 WO2025076039 A1 WO 2025076039A1 US 2024049528 W US2024049528 W US 2024049528W WO 2025076039 A1 WO2025076039 A1 WO 2025076039A1
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composition
cpaf
subject
agonist
administering
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Lee Antoinette DARVILLE
Taylor POSTON
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University of North Carolina at Chapel Hill
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    • 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
    • A61P31/04—Antibacterial agents
    • 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
    • A61K39/118—Chlamydiaceae, e.g. Chlamydia trachomatis or Chlamydia psittaci
    • 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
    • A61K2039/54—Medicinal preparations containing antigens or antibodies characterised by the route of administration
    • A61K2039/541—Mucosal route
    • A61K2039/543—Mucosal route intranasal
    • 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
    • A61K2039/545—Medicinal preparations containing antigens or antibodies characterised by the dose, timing or administration schedule
    • 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
    • A61K2039/555—Medicinal preparations containing antigens or antibodies characterised by a specific combination antigen/adjuvant
    • A61K2039/55511—Organic adjuvants
    • A61K2039/55561—CpG containing adjuvants; Oligonucleotide containing adjuvants
    • 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
    • A61K2039/555—Medicinal preparations containing antigens or antibodies characterised by a specific combination antigen/adjuvant
    • A61K2039/55511—Organic adjuvants
    • A61K2039/55566—Emulsions, e.g. Freund's adjuvant, MF59
    • 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
    • A61K2039/57—Medicinal preparations containing antigens or antibodies characterised by the type of response, e.g. Th1, Th2
    • A61K2039/572—Medicinal preparations containing antigens or antibodies characterised by the type of response, e.g. Th1, Th2 cytotoxic response
    • 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
    • A61K2039/57—Medicinal preparations containing antigens or antibodies characterised by the type of response, e.g. Th1, Th2
    • A61K2039/575—Medicinal preparations containing antigens or antibodies characterised by the type of response, e.g. Th1, Th2 humoral response

Definitions

  • compositions comprising chlamydial protease-like activity factor (CPAF) or an antigenic fragment thereof and a stimulator of interferon genes (STING) agonist, and methods of use of the same in raising an immune response and/or in vaccinating a subject against a Chlamydia trachomatis infection.
  • CPAF chlamydial protease-like activity factor
  • STING stimulator of interferon genes
  • Genital Chlamydia trachomatis (CT) infection and associated diseases remain a significant global health burden, with an estimated 131 million new cases occurring annually. In the United States, >1 million women are infected annually, and direct treatment costs exceed $500 million. Antibiotic treatment efficacy is limited, primarily because >70% of infections are asymptomatic and are thus left untreated. Bacterial ascension from the cervix to the endometrium and oviducts induces inflammation that leads to the clinical syndrome of pelvic inflammatory disease (PID) in 10% of infected women; and even women without symptoms may have endometritis or subclinical PID.
  • PID pelvic inflammatory disease
  • one aspect of the invention relates to a composition
  • a composition comprising a CPAF or an antigenic fragment thereof and a STING agonist.
  • the composition comprises at least one additional adjuvant.
  • the at least one additional adjuvant is a toll-like receptor (TLR) agonist and/or an oil-in-water emulsion.
  • the composition is a pharmaceutical composition comprising a pharmaceutically acceptable carrier.
  • the composition is suitable for mucosal administration.
  • Another aspect of the invention is a method of raising an immune response against CT in a subject, said method comprising administering an effective amount of a composition as described herein, thereby raising an immune response.
  • Another aspect of the invention is a method of vaccinating a subject against a CT infection, said method comprising administering a therapeutically effective amount of the composition as described herein, thereby vaccinating the subject.
  • FIG. 3 panel A is a graph showing the number of SFU/10 6 in splenocytes isolated from C57BL/6 mice that had previously cleared a CM972 (a live attenuated Chlamydia muridarum (C. muridarum CM) strain) infection followed by a CM001 (a virulent CM strain) infection (CM972+CM001) and sacrificed 30 days post-clearance; splenocytes were stimulated with 5 pg/mL of the stated antigens and the response was measured by IFNy ELIspot assay; **** indicates p-value ⁇ 0.0001 by one-way ANOVA.
  • CM972 a live attenuated Chlamydia muridarum (C. muridarum CM) strain
  • CM001 a virulent CM strain infection
  • **** indicates p-value ⁇ 0.0001 by one-way ANOVA.
  • panel B is a density scatter plot showing the ICS measured IFNy+ TNFa+ responses in CD4 and CD8 T cells isolated from CM972+CM001 mice that were stimulated with either control media or CPAF overlapping peptides (OLP), sequences of 18 amino acids that overlap one another by 15 amino acids.
  • Fig. 3 panel C is a graph showing the percent of naive or CM972 vaccinated CD4 T cells harvested from mouse genital tracts that produced a IFNy+ TNFa+ response 7 days after CM001 challenge; error bars represent the mean ⁇ one standard deviation.
  • Fig. 5 is a graph showing the deconvoluted mass spectrum of intact protein analysis by LC-MS showed the three major forms of S491 A CPAF: the peak at 26,927.9 Daltons is the N- terminal clipped fragment; the peak at 41,419.3 Daltons is the C-terminal fragment; and the peak at 68,329.0 Daltons is the full-length protein.
  • the Y-axis indicates the mass spectrometry signal intensity, the X-axis indicates the mass of the protein or protein fragments in Daltons.
  • Fig. 6 panels A-C are a series of graphs showing the expression level of IFNy, IL-6, and TNFa in the lung at 3 hours, 24 hours, and 1 week post immunization, as indicated. Fig.
  • Group 1 was immunized with CPAF only;
  • Group 2 was immunized with CPAF + CpG + CD A;
  • Group 3 was immunized with CPAF + CpG + CD A + AS03;
  • Group 4 was immunized with CpG + CD A + AS03;
  • Group 5 was immunized with CPAF + 2-Bxy-Dopa (a TLR7/8 agonist conjugated to dopamine).
  • Fig. 9, panel A is a series of graphs showing the flow cytometric gating strategy for detection of CPAF-specific memory CD4 and CD8 T cell responses.
  • the term “consists essentially of’ (and grammatical variants), as applied to a polynucleotide or polypeptide sequence of this invention, means a polynucleotide or polypeptide that consists of both the recited sequence (e.g., SEQ ID NO) and a total of ten or less (e.g., 1, 2, 3, 4, 5, 6, 7, 8, 9, or 10) additional nucleotides or amino acids on the 5’ and/or 3’ or N-terminal and/or C-terminal ends of the recited sequence or between the two ends (e.g., between domains) such that the function of the polynucleotide or polypeptide is not materially altered.
  • SEQ ID NO a polynucleotide or polypeptide that consists of both the recited sequence (e.g., SEQ ID NO) and a total of ten or less (e.g., 1, 2, 3, 4, 5, 6, 7, 8, 9, or 10) additional nucleotides or amino acids on the 5
  • the total of ten or less additional nucleotides or amino acids includes the total number of additional nucleotides or amino acids added together.
  • inhibit or “reduce” or grammatical variations thereof as used herein refers to a decrease or diminishment in the specified level or activity of at least about 15%, 25%, 35%, 40%, 50%, 60%, 75%, 80%, 90%, 95% or more. In particular embodiments, the inhibition or reduction results in little or essentially no detectible activity (at most, an insignificant amount, e.g., less than about 10% or even 5%).
  • a “therapeutically effective” or “treatment effective” amount as used herein is an amount that provides some improvement or benefit to the subject.
  • a “therapeutically effective” or “treatment effective” amount is an amount that will provide some alleviation, mitigation, or decrease in at least one clinical symptom in the subject (e.g., in the case of raising an immune response, activating or increasing the number of immune cells known to produce an immune response).
  • the therapeutic effects need not be complete or curative, as long as some benefit is provided to the subject.
  • prevent means to delay or inhibit the onset of a disease.
  • the terms are not meant to require complete abolition of disease, and encompass any type of prophylactic treatment to reduce the incidence of the condition or delay the onset of the condition.
  • a “prevention effective” amount as used herein is an amount that is sufficient to prevent and/or delay the onset of a disease, disorder and/or clinical symptoms in a subject and/or to reduce and/or delay the severity of the onset of a disease, disorder and/or clinical symptoms in a subject relative to what would occur in the absence of the methods of the invention.
  • the level of prevention need not be complete, as long as some benefit is provided to the subject.
  • fragment as applied to a polypeptide, will be understood to mean an amino acid sequence of reduced length relative to a reference polypeptide or amino acid sequence and comprising, consisting essentially of, and/or consisting of an amino acid sequence of contiguous amino acids identical or almost identical (e.g., 90%, 92%, 95%, 98%, 99% identical) to the reference polypeptide or amino acid sequence.
  • a polypeptide fragment according to the invention may be, where appropriate, included in a larger polypeptide of which it is a constituent.
  • such fragments can comprise, consist essentially of, and/or consist of peptides having a length of at least about 4, 6, 8, 10, 12, 15, 20, 25, 30, 35, 40, 45, 50, 75, 100, 150, 200, or more consecutive amino acids of a polypeptide or amino acid sequence according to the invention.
  • an “isolated” polypeptide means a polypeptide that is separated or substantially free from at least some of the other components of the naturally occurring organism or virus, for example, the cell or viral structural components or other polypeptides or nucleic acids commonly found associated with the polypeptide.
  • modified refers to a sequence that differs from a wildtype sequence due to one or more deletions, additions, substitutions, or any combination thereof.
  • sequence identity refers to the extent to which two optimally aligned polynucleotide or polypeptide sequences are invariant throughout a window of alignment of components, e.g., nucleotides or amino acids. “Identity” can be readily calculated by known methods including, but not limited to, those described in: Computational Molecular Biology (Lesk, A. M., ed.) Oxford University Press, New York (1988); Biocomputing: Informatics and Genome Projects (Smith, D. W ., ed.) Academic Press, New York (1993); Computer Analysis of Sequence Data, Part I (Griffin, A. M., and Griffin, H.
  • the term “substantially identical” or “corresponding to” means that two nucleic acid or polypeptide sequences have at least 60%, 70%, 80% or 90% sequence identity. In some embodiments, the two nucleic acid or polypeptide sequences can have at least 85%, 90%, 95%, 96%, 97%, 98%, 99% or 100% of sequence identity.
  • vaccinate and “immunize” are used interchangeably herein to mean administering a compound and/or composition (e.g., a vaccine) in a prevention effective amount to a subject.
  • a vaccine may prevent, delay, and/or reduce the severity of a disease, disorder and/or clinical symptoms in a subject after administration to said subject relative to what would occur in the absence of the methods of the invention.
  • the antigenic fragments of the CPAF are from about 5 to about 50 amino acids in length (e.g., about 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, 20, 21, 22, 23, 24, 25, 30, 35, 40, 35, or 50 amino acids in length).
  • the composition comprising the antigenic fragments of the CPAF comprises one or more antigenic fragments (e.g., about 2, 3, 4, 5, 10, 15, 20, 25, 30, 35, 40, 45, 50, 55, 60, 65, 70, 75, 80, 85, 90, 95, 100, 105, 110, 115, 120, 125, or more antigenic fragments).
  • the STING agonist is present in the composition in a concentration of about 0.1 pg/pL to about 50 pg/pL (e.g., about 0.1, 0.2, 0.3, 0.4, 0.5, 0.6, 0.7, 0.8, 0.9, 1, 1.25, 1.5, 1.75, 2, 2.5, 3, 3.5, 4, 4.5, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, 20, 25, 30, 35, 40, 45, or about 50 pg/pL or any range therein).
  • the STING agonist can be any STING agonist known in the art.
  • the oil-in-water emulsion is present in the composition in an amount of about 10% to about 75% by weight of the composition (e.g., about 10%, 11%, 12%, 13%, 14%, 15%, 16%, 17%, 18%, 19%, 20%, 25%, 30%, 35%, 40%, 45%, 50%, 55%, 60%, 65%, 70%, or about 75% by weight of the composition or any range therein).
  • a composition of the present invention is administered to a subject in an amount of about 1 pL to about 1 mL (e.g., about 1 pL, 2 pL, 3 pL, 4 pL, 5 pL, 10 pL, 15 pL, 20 pL, 25 pL, 30 pL, 35 pL, 40 pL, 45 pL, 50 pL, 100 pL, 150 pL, 200 pL, 250 pL, 300 pL, 350 pL, 400 pL, 450 pL, 500 pL, 600 pL, 700 pL, 800 pL, 900 pL, to about 1 mL).
  • compositions of the present invention may be administered to a subject by any suitable method including, but not limited to, intranasal administration (e.g., sprays or gels); oral administration (e.g., lozenges, sprays, or gels), e.g., sublingual sprays or gels; anal administration (e.g., gels or suppositories); ocular administration (e.g., eye drops or gels); intramuscular administration (e.g., intramuscular injection); subcutaneous administration (e.g., subcutaneous injection); subdermal administration (e.g., subdermal injection); intravenous administration (e.g., intravenous injection); and/or vaginal administration (e.g., gels or suppositories).
  • the administration is mucosal administration.
  • mice inoculated vaginally with CM recapitulate immune mediators of protection and fallopian tube pathology observed with severe CT infection in cisgender women.
  • This pathology specifically oviduct scarring and fibrosis with post-obstructive dilatation or hydrosalpinx, provides a robust model for vaccine testing.
  • CM stock populations contain subpopulations of genetic variants expressing phenotypic differences 48 . Inoculation of mice with different plaque-purified clonal isolates from these stocks results in infections of varying severity 26 .
  • the UNC-CVI CT vaccine antigen discovery pipeline evaluated antibody and T cell responses in CT-exposed women enrolled in the T cell Response Against Chlamydia (TRAC) study 6, 5 while also profiling chlamydial gene expression in infected TRAC2 participants. Screening T cells from 30 CT-exposed TRAC participants for reactivity against pooled peptides representing 33 CT proteins identified CPAF as the top CD4 T cell antigen tested to date. T cell responses for 21 antigens are depicted in Fig. 1, panel A and Fig. 1, panel B; 12 additional antigens tested negatively in all individuals.
  • T cell responses for 21 antigens are depicted in Fig. 1, panel A and Fig. 1, panel B; 12 additional antigens tested negatively in all individuals.
  • CDA Bacterial agonists such as CDA show promise as adjuvants with a good safety record for mice and humans 15 ' 17 .
  • CDA activates the cytosolic STING pathway that elicits inflammatory cytokines and interferons to drive robust Thl/17 responses 18 ' 21 .
  • CpG and AS03 have shown effectiveness in eliciting CD4 T cell responses in humans 22 ' 24
  • Chlamydia Chlamydia muridarum
  • Protease Activity Factor (CPAF Cm) antigen was expressed using XpressCF® (Sutro Biopharma).
  • the catalytic serine at position 491 was changed to alanine.
  • the CPAF Cm clone was a gift from Jon Harris (Queensland University of Technology). After cell-free expression, the protein was purified by Ni affinity chromatography (Cytiva).
  • Proteins were prepared in 2x-Laemmli sample buffer (Bio-Rad, Philadelphia, PA) added with 5% P-mercaptoethanol and denatured by heating at 95 °C for 5 min. The denatured protein samples (20 pl) were loaded onto 12% precasted polyacrylamide gels (Bio-Rad). For western blot analysis, SDS-PAGE-run samples were then transferred into the nitrocellulose membrane using Trans-Blot Turbo Transfer Packs (Bio-Rad).
  • the membrane was blocked with PBS containing 0.5% Tween-20 (PBS-T) and 3% BSA, and incubated with anti-His tag antibodies (#MA1-21315, Invitrogen; diluted 1 : 5,000 in PBS-T) or murine anti-CPAF immune sera (pooled from mice immunized with CPAF protein; diluted 1: 1000 in PBS-T) overnight at 4°C.
  • the membrane was washed with PBS-T and incubated with Horseradish Peroxidase (HRP)-labeled goat anti-mouse IgG (#5220-0460, KPL SeraCare, Gaithersburg, MD) diluted 1 : 10,000 in PBS-T for 1 hour at room temperature.
  • HRP Horseradish Peroxidase
  • mice were anesthetized intraperitoneally with 250 pL of Nembutal (50 mg/mL) and then immunized intranasally on day 0 with 15 pg adjuvanted CPAF or CPAF alone in a 12 pl volume (6 pl/nare). Mice were intranasally boosted 30 days later with the same vaccine formulation(s).
  • IFNy spot-forming cells were detected by staining membranes with anti-mouse IFNy biotin (1 pg/ml; R46A2) followed by streptavidin-alkaline phosphatase (1 pg/ml) and developed with NBT/BCIP substrate solution (Thermo Fisher). Spots were enumerated on an AID ELISpot reader.
  • Serum from vaccinated C57BL/6 mice were assayed for CPAF-specific IgG, IgGl, IgG2b and IgG2c antibody responses.
  • ELISA plates were coated overnight at 4 °C with 10 pg/ml recombinant MBP-CPAF (from John Harris, Queensland University of Technology) diluted in 0.5M NaHCO3. Plates were washed with PBS-Tween. After blocking with 2% BSA PBS-Tween for 1 hour at 37 °C, samples were serially diluted and incubated for 1 hour at 37 °C. Internal controls were generated using reference serum. Plates were washed with PBS- Tween.
  • a goat anti-mouse horseradish peroxidase-conjugated secondary antibody was added (Southern Biotech) and incubated for 1 hour at 37 °C.
  • Goat anti-mouse IgG was added at a 1 :4,000 dilution and IgGl, IgG2b, and IgG2c were added at a 1 :500 dilution.
  • the plates were developed using TMB substrate solution (ThermoScientific) for a maximum of 20 minutes. The reaction was stopped using 0.5M H2SO4 and OD was read at 450 nm.
  • the cutoff for detecting a specific antibody response was defined by a value greater than the mean+3 standard deviations of the non-specific antibody values.
  • mice at least 8 weeks old were subcutaneously injected with 2.5 mg medroxyprogesterone (Depo-Provera; Upjohn) 5-7 days prior to infection to induce a state of anestrous.
  • Mice were intravaginally inoculated with U 10 5 inclusion forming units (IFU) CM006 diluted in 30 pl sucrose-sodium phosphate-glutamic acid buffer 28 days post booster immunization. Mice were monitored for cervicovaginal shedding via endocervical swabs 28 , and IFUs were calculated, as described previously 29 . Animal welfare was monitored daily.
  • IFU inclusion forming units
  • the S491A mutation in the tail-specific protease domain renders the CPAF protease inactive and incapable of natural auto-processing and proteolysis 30, 31 .
  • cell-free expression yielded full-length CPAF and a clipped form consisting of N- and C-terminal fragments (Fig. 4, panel A).
  • Mass spectrometry revealed the clip site to be at K232 (Fig. 5, Table 2), three amino acids from the native auto-processing site.
  • the K232Q mutation produced a full-length Cm CPAF protein (Fig. 1, panel B). Both Cm CPAF variants were applied to an analytical sizing column and eluted as a single Gaussian peak (Fig. 1, panel C).
  • the full-length wild-type and K232Q variant had the same retention time demonstrating similar folding and dimerization.
  • the clipped form was used for vaccine studies.
  • Intranasal immunization with CP AF plus CDA induces a memory CD4 T cell response characterized by the production of IL-17 A or IFNy.
  • mice immunized intranasally and boosted with a second dose thirty days later were assessed for systemic antibody and T cell responses ten days post-boost (Fig. 7, panel A).
  • Most mice immunized with CPAF alone, CPAF plus CDA, or CPAF plus CpG/CDA/AS03 had low to undetectable serum antibody titers with no significant differences between the groups (Fig. 7, panel B).
  • Thl-biased IgG2b and IgG2c were detected in a few individual mice, while IgGl was not detected.
  • STING pathway agonists have demonstrated an excellent safety profile in mice and humans 15, 16 and have elicited strong T cell immunogenicity and protection against bacterial pathogens like Mycobacterium tuberculosis 32, 33 and Bordetella pertussis 34, 35 . However, their efficacy has not been tested against Chlamydia infection. Without wishing to be bound by any particular theory, we hypothesized that intranasal immunization with the immunodominant secreted antigen CPAF combined with CDA would induce a memory CD4 T cell response and protect female mice against genital Chlamydia infection.
  • Fc-mediated antigen presentation could be enhanced by CPAF-specific IgG, resulting in boosted CD4 T cell responses 38 .
  • CPAF-specific T cells were characterized by a CD4-dominant response, consistent with other studies using protein immunization 40 .
  • the CD4 response demonstrated a mixed profile of IFNy ⁇ TNFa and IL-17A ⁇ TNFa producing cells, like those achieved in mice with the subcutaneously delivered MOMP -based immunogen CTH522 adjuvanted with CAF01 42 .
  • the immunophenotypic T cell expression of IFNy i TNFa is routinely measured in Chlamydia studies, while detecting IL-17A responses is less common 43 . It is unclear if there is a need for de facto or ex-Thl7 cells in vaccine-elicited protection against Chlamydia genital infection, as observed for other bacterial pathogens like Klebsiella spp. and Mycobacterium tuberculosis 44, 45 . We also observed a low frequency of TNFa single-positive CD8 T cells. These monofunctional cells are shown to be dispensable for protection 25 .
  • Murthy AK Chambers JP, Meier PA, Zhong G, Arulanandam BP: Intranasal vaccination with a secreted chlamydial protein enhances resolution of genital Chlamydia muridarum infection, protects against oviduct pathology, and is highly dependent upon endogenous gamma interferon production. Infect Immun 2007, 75:666-76.
  • Humphries F Shmuel-Galia L, Jiang Z, Wilson R, Landis P, Ng SL, Parsi KM, Maehr R, Cruz J, Morales-Ramos A, Ramanjulu JM, Bertin J, Pesiridis GS, Fitzgerald KA: A diamidobenzimidazole STING agonist protects against SARS-CoV-2 infection. Sci Immunol 2021, 6.

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Abstract

La présente invention concerne des compositions comprenant un facteur d'activité chlamydia de type protéase (CPAF) ou un fragment antigénique de celui-ci et un stimulateur d'agoniste de gènes de l'interféron (STING) utiles pour déclencher une réponse immunitaire chez un sujet et vacciner le sujet contre une infection par Chlamydia trachomatis. De plus, la composition peut en outre comprendre un agoniste de TLR et/ou une émulsion huile dans l'eau de façon à augmenter l'efficacité de l'immunogène CPAF. La présente invention concerne également des procédés d'administration de la composition, y compris l'administration par voie muqueuse.
PCT/US2024/049528 2023-10-03 2024-10-02 Facteur d'activité chlamydia de type protéase et compositions d'adjuvant et leurs utilisations Pending WO2025076039A1 (fr)

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Citations (1)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
WO2006104890A2 (fr) * 2005-03-31 2006-10-05 Glaxosmithkline Biologicals Sa Vaccins destines a lutter contre une infection a chlamydia

Patent Citations (1)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
WO2006104890A2 (fr) * 2005-03-31 2006-10-05 Glaxosmithkline Biologicals Sa Vaccins destines a lutter contre une infection a chlamydia

Non-Patent Citations (4)

* Cited by examiner, † Cited by third party
Title
BARKER JEFFREY R., KOESTLER BENJAMIN J., CARPENTER VICTORIA K., BURDETTE DARA L., WATERS CHRISTOPHER M., VANCE RUSSELL E., VALDIVI: "STING-Dependent Recognition of Cyclic di-AMP Mediates Type I Interferon Responses during Chlamydia trachomatis Infection", MBIO, AMERICAN SOCIETY FOR MICROBIOLOGY, US, vol. 4, no. 3, 1 July 2013 (2013-07-01), US , XP093302879, ISSN: 2161-2129, DOI: 10.1128/mBio.00018-13 *
DUDIAK BRIANNE M., MAKSIMCHUK KENNETH R., BEDNAR MARIA M., PODRACKY CHRISTOPHER J., BURG JONATHAN M., NGUYEN TRI M., NWOGBO FELIX : "Insights into the Autoproteolytic Processing and Catalytic Mechanism of the Chlamydia trachomatis Virulence-Associated Protease CPAF", BIOCHEMISTRY (EASTON), AMERICAN CHEMICAL SOCIETY, UNITED STATES, vol. 58, no. 33, 20 August 2019 (2019-08-20), United States, pages 3527 - 3536, XP093302876, ISSN: 0006-2960, DOI: 10.1021/acs.biochem.9b00522 *
SNAVELY EMILY A., KOKES MARCELA, DUNN JOE DAN, SAKA HECTOR A., NGUYEN BIDONG D., BASTIDAS ROBERT J., MCCAFFERTY DEWEY G., VALDIVIA: "Reassessing the role of the secreted protease CPAF in Chlamydia trachomatis infection through genetic approaches", PATHOGENS AND DISEASE, OXFORD UNIVERSITY PRESS, GB, vol. 71, no. 3, 1 August 2014 (2014-08-01), GB , pages 336 - 351, XP093302878, ISSN: 2049-632X, DOI: 10.1111/2049-632X.12179 *
WEBSTER STEVE J., BRODE SVEN, ELLIS LOU, FITZMAURICE TIMOTHY J., ELDER MATTHEW J., GEKARA NELSON O., TOURLOMOUSIS PANAGIOTIS, BRYA: "Detection of a microbial metabolite by STING regulates inflammasome activation in response to Chlamydia trachomatis infection", PLOS PATHOGENS, PUBLIC LIBRARY OF SCIENCE, US, vol. 13, no. 6, 1 June 2017 (2017-06-01), US , pages e1006383, XP093302875, ISSN: 1553-7374, DOI: 10.1371/journal.ppat.1006383 *

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