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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

Authors :
Emma Lorenzen
Vanessa Contreras
Anja W. Olsen
Peter Andersen
Delphine Desjardins
Ida Rosenkrands
Helene Bæk Juel
Benoit Delache
Sebastien Langlois
Constance Delaugerre
Christophe Joubert
Nathalie Dereuddre-Bosquet
Cécile Bébéar
Bertille De Barbeyrac
Arabella Touati
Paul F. McKay
Robin J. Shattock
Roger Le Grand
Frank Follmann
Jes Dietrich
Source :
Lorenzen, E, Contreras, V, Olsen, A W, Andersen, P, Desjardins, D, Rosenkrands, I, Juel, H B, Delache, B, Langlois, S, Delaugerre, C, Joubert, C, Dereuddre-Bosquet, N, Bébéar, C, De Barbeyrac, B, Touati, A, McKay, P F, Shattock, R J, Le Grand, R, Follmann, F & Dietrich, J 2022, ' 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 ', Frontiers in Immunology, vol. 13, 1057375 . https://doi.org/10.3389/fimmu.2022.1057375
Publication Year :
2022
Publisher :
Frontiers Media SA, 2022.

Abstract

It is of international priority to develop a vaccine against sexually transmittedChlamydia trachomatisinfections to combat the continued global spread of the infection. The optimal immunization strategy still remains to be fully elucidated. The aim of this study was to evaluate immunization strategies in a nonhuman primate (NHP) model. Cynomolgus macaques (Macaqua fascicularis) were immunized following different multi-component prime-boost immunization-schedules and subsequently challenged withC. trachomatisSvD in the lower genital tract. The immunization antigens included the recombinant protein antigen CTH522 adjuvanted with CAF01 or aluminium hydroxide, MOMP DNA antigen and MOMP vector antigens (HuAd5 MOMP and MVA MOMP). All antigen constructs were highly immunogenic raising significant systemicC. trachomatis-specific IgG responses. In particularly the CTH522 protein vaccinated groups raised a fast and strong pecificsIgG in serum. The mapping of specific B cell epitopes within the MOMP showed that all vaccinated groups, recognized epitopes near or within the variable domains (VD) of MOMP, with a consistent VD4 response in all animals. Furthermore, serum from all vaccinated groups were able toin vitroneutralize both SvD, SvE and SvF. Antibody responses were reflected on the vaginal and ocular mucosa, which showed detectable levels of IgG. Vaccines also inducedC. trachomatis-specific cell mediated responses, as shown byin vitrostimulation and intracellular cytokine staining of peripheral blood mononuclear cells (PBMCs). 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 withC. trachomatisSvD, 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.

Details

ISSN :
16643224
Volume :
13
Database :
OpenAIRE
Journal :
Frontiers in Immunology
Accession number :
edsair.doi.dedup.....a07d14fb4a43d45d43dda10b05c00833
Full Text :
https://doi.org/10.3389/fimmu.2022.1057375