CTH522 / Statens Serum Institut, Imperial College London - LARVOL DELTA

Post-exposure vaccine protection of CTH522/CAF®01 against reinfection with Chlamydia trachomatis requires Th1/Th17 but not Th2-immunity. (PubMed, NPJ Vaccines) - "Using this model, we show that UV-SvD/CAF®01 and CTH522/CAF®01 as post-exposure parenteral vaccines, but not CTH522/AlOH, protected against reinfection. As CTH522/CAF®01 also reduced the gross pathology score post reinfection, this suggests that CTH522/CAF®01 is both protective and safe as a post-exposure vaccine."

Journal • Infectious Disease

Innovative Approach for the Clinical Development of a Chlamydia trachomatis Vaccine Through a Human-Challenge Model in Women. (PubMed, Int J Infect Dis) - "Recent Phase 1 trials of the C. trachomatis vaccine candidate CTH522 in both women and men have shown that the adjuvanted and non-adjuvanted formulations are safe and elicit systemic (IgG) and mucosal (IgA) antibodies, as well as vaccine-specific cell-mediated immunity. In advance of a standard Phase 2 randomized controlled trial to determine the vaccine's efficacy, this perspective advocates for using a carefully and ethically designed human challenge model as an innovative approach to assess a vaccine's ability to prevent infection and its impact on tubal immunopathogenesis in breakthrough infections. Such models could accelerate vaccine development by providing critical insights, making it essential for stakeholders to consider this approach and expedite the long-awaited chlamydia vaccine."

Journal • Infectious Disease

Intradermal administration of novel particulate Chlamydia trachomatis vaccine candidates drives protective immune responses. (PubMed, Biomed Pharmacother) - "Importantly, intradermal immunization with PB-CTH522-SP significantly reduced bacterial counts following C. trachomatis genital challenge. These data highlight the potential of the PB-based platform for the development of C. trachomatis vaccines."

Journal • Infectious Disease • CD4 • CD8 • IFNG • IL17A

Viral Vector-Based Chlamydia trachomatis Vaccines Encoding CTH522 Induce Distinct Immune Responses in C57BL/6J and HLA Transgenic Mice. (PubMed, Vaccines (Basel)) - "This research contributes to the development of effective vaccines by highlighting the importance of careful antigen design and the selection of appropriate animal models to study specific vaccine-induced immune responses. Future studies should investigate whether these immune responses provide protection in humans and should explore different routes of immunization, including mucosal and systemic immunization."

Journal • Preclinical • Viral vector • Infectious Disease • CD4 • CD8

Human antibody signatures towards the Chlamydia trachomatis major outer membrane protein after natural infection and vaccination. (PubMed, EBioMedicine) - "These data provide insights into the role of antibodies against MOMP VD4 induced after infection and vaccination, and show that their functionality differs. The induction of functional VD4-specific antibodies in vaccine recipients mimics previous results from animal models."

Journal • Infectious Disease

An investigation of trachoma vaccine regimens by the chlamydia vaccine CTH522 administered with cationic liposomes in healthy adults (CHLM-02): a phase 1, double-blind trial. (PubMed, Lancet Infect Dis) - P1 | "CTH522, adjuvanted with CAF01 or CAF09b, is safe and immunogenic, with 85 μg CTH522-CAF01 inducing robust serum IgG binding titres. Intradermal vaccination conferred systemic IgG neutralisation breadth, and topical ocular administration increased ocular IgA formation. These findings indicate CTH522 vaccine regimens against ocular trachoma and urogenital chlamydia for testing in phase 2, clinical trials."

Journal • P1 data • Infectious Disease • Ophthalmology

Intranasal delivery of Salmonella OMVs decorated with Chlamydia trachomatis antigens induces specific local and systemic immune responses. (PubMed, Hum Vaccin Immunother) - "Notably, the OMV-CTH522 vaccine also induced the production of spleen-derived CD8+ T cells expressing IFN-γ. In conclusion, these results highlight the potential of OMV-based C. trachomatis vaccines for successful use in future challenge studies and demonstrate the suitability of our modular OMV platform for intranasal vaccine applications."

Journal • Infectious Disease • CD4 • CD8 • IFNG • IL17A

Immune signature of Chlamydia vaccine CTH522/CAF®01 translates from mouse-to-human and induces durable protection in mice. (PubMed, Nat Commun) - "Finally, we demonstrate long-lasting immunity and protection of mice one year after vaccination. Based on the results obtained in the present study, we propose to further investigate CTH522/CAF®01 in a phase IIb study."

Journal • Preclinical • Infectious Disease

Co-adjuvanting DDA/TDB liposomes with a TLR7 agonist allows for IgG2a/c class-switching in the absence of Th1 cells. (PubMed, NPJ Vaccines) - "When testing this adjuvant in adult mice using the recombinant Chlamydia trachomatis (C.t.) vaccine antigen CTH522, it similarly enhanced IgG2a/c responses compared to DDA/TDB, but surprisingly reduced the magnitude of the IFN-γ+Th1 response in a TLR7 agonist dose-dependent manner...Mixed bone marrow chimeras further demonstrated that this adjuvant did not require Th1 cells for IgG2a/c switching, but rather facilitated TLR7-dependent T-bet programming directly in B cells. This study underlines that adjuvant-directed IgG2a/c class-switching in vivo can occur in the absence of T-cell help, via direct activation of TLR7 on B cells and positions DDA/TDB/3M-052 as a powerful adjuvant capable of eliciting type I-like immunity in B cells without strong induction of Th1 responses."

Journal • Infectious Disease • IFNG

Multi-component prime-boost Chlamydia trachomatis vaccination regimes induce antibody and T cell responses and accelerate clearance of infection in a non-human primate model. (PubMed, Front Immunol) - "In general, the protein (CTH522) vaccinated groups established a multifunctional CD4 T cell response, whereas the DNA and Vector vaccinated groups also established a CD8 T cells response. Following vaginal challenge with C. trachomatis SvD, several of the vaccinated groups showed accelerated clearance of the infection, but especially the DNA group, boosted with CAF01 adjuvanted CTH522 to achieve a balanced CD4/CD8 T cell response combined with an IgG response, showed accelerated clearance of the infection."

Journal • Preclinical • Immunology • Infectious Disease • CD4 • CD8

Oral vaccination using microdevices to deliver α-GalCer adjuvanted vaccine afford mucosal immunity. (PubMed, J Control Release) - "Here, we test MCs, for oral delivery of the C. trachomatis vaccine candidate CTH522, in combination with effective mucosal adjuvants...This indicates that mice is not a suitable animal model for evaluation of MCs. These data should be taken into consideration in future in vivo trials with this and similar technologies, where larger animals might be a necessity for proof-of-concept studies."

Journal • Cholera • Gastrointestinal Disorder • Immunology • IFNG

CHLM-02: Safety and Immunogenicity of a Chlamydia Vaccine CTH522 (clinicaltrials.gov) - P1 | N=65 | Completed | Sponsor: Statens Serum Institut | Recruiting ➔ Completed

Trial completion • Infectious Disease • Ophthalmology