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
It is of international priority to develop a vaccine against sexually transmitted Chlamydia trachomatis infections 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 strate...
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Frontiers Media S.A.
2022-11-01
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| Series: | Frontiers in Immunology |
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| Online Access: | https://www.frontiersin.org/articles/10.3389/fimmu.2022.1057375/full |
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| author | 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 |
| author_facet | 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 |
| author_sort | Emma Lorenzen |
| collection | DOAJ |
| description | It is of international priority to develop a vaccine against sexually transmitted Chlamydia trachomatis infections 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 with C. trachomatis SvD 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 systemic C. 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 to in vitro neutralize both SvD, SvE and SvF. Antibody responses were reflected on the vaginal and ocular mucosa, which showed detectable levels of IgG. Vaccines also induced C. trachomatis-specific cell mediated responses, as shown by in vitro stimulation 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 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. |
| first_indexed | 2024-04-11T06:43:51Z |
| format | Article |
| id | doaj.art-8eba49251cfe46ee8889846d67ba7fb9 |
| institution | Directory Open Access Journal |
| issn | 1664-3224 |
| language | English |
| last_indexed | 2024-04-11T06:43:51Z |
| publishDate | 2022-11-01 |
| publisher | Frontiers Media S.A. |
| record_format | Article |
| series | Frontiers in Immunology |
| spelling | doaj.art-8eba49251cfe46ee8889846d67ba7fb92022-12-22T04:39:25ZengFrontiers Media S.A.Frontiers in Immunology1664-32242022-11-011310.3389/fimmu.2022.10573751057375Multi-component prime-boost Chlamydia trachomatis vaccination regimes induce antibody and T cell responses and accelerate clearance of infection in a non-human primate modelEmma Lorenzen0Vanessa Contreras1Anja W. Olsen2Peter Andersen3Delphine Desjardins4Ida Rosenkrands5Helene Bæk Juel6Benoit Delache7Sebastien Langlois8Constance Delaugerre9Christophe Joubert10Nathalie Dereuddre-Bosquet11Cécile Bébéar12Bertille De Barbeyrac13Arabella Touati14Paul F. McKay15Robin J. Shattock16Roger Le Grand17Frank Follmann18Jes Dietrich19Chlamydia Vaccine Research, Department of Infectious Disease Immunology, Statens Serum Institut, Copenhagen, DenmarkUniversité Paris-Saclay, Inserm, Commissariat à l'Énergie Atomique et aux Énergies Alternatives (CEA), Center for Immunology of Viral, Auto-immune, Hematological and Bacterial diseases (IMVA-HB/IDMIT), Fontenay-aux-Roses & Le Kremlin-Bicêtre, FranceChlamydia Vaccine Research, Department of Infectious Disease Immunology, Statens Serum Institut, Copenhagen, DenmarkNovo Nordisk Foundation, Infectious Disease, Hellerup, DenmarkUniversité Paris-Saclay, Inserm, Commissariat à l'Énergie Atomique et aux Énergies Alternatives (CEA), Center for Immunology of Viral, Auto-immune, Hematological and Bacterial diseases (IMVA-HB/IDMIT), Fontenay-aux-Roses & Le Kremlin-Bicêtre, FranceChlamydia Vaccine Research, Department of Infectious Disease Immunology, Statens Serum Institut, Copenhagen, DenmarkNovo Nordisk Foundation, Center for Basic Metabolic Research, Copenhagen, DenmarkUniversité Paris-Saclay, Inserm, Commissariat à l'Énergie Atomique et aux Énergies Alternatives (CEA), Center for Immunology of Viral, Auto-immune, Hematological and Bacterial diseases (IMVA-HB/IDMIT), Fontenay-aux-Roses & Le Kremlin-Bicêtre, FranceUniversité Paris-Saclay, Inserm, Commissariat à l'Énergie Atomique et aux Énergies Alternatives (CEA), Center for Immunology of Viral, Auto-immune, Hematological and Bacterial diseases (IMVA-HB/IDMIT), Fontenay-aux-Roses & Le Kremlin-Bicêtre, FranceLaboratory of Virology, Hôpital Saint-Louis, Assistance Publique Hôpitaux de Paris, Université de Paris, Paris Cité, Paris, FranceUniversité Paris-Saclay, Inserm, Commissariat à l'Énergie Atomique et aux Énergies Alternatives (CEA), Center for Immunology of Viral, Auto-immune, Hematological and Bacterial diseases (IMVA-HB/IDMIT), Fontenay-aux-Roses & Le Kremlin-Bicêtre, FranceUniversité Paris-Saclay, Inserm, Commissariat à l'Énergie Atomique et aux Énergies Alternatives (CEA), Center for Immunology of Viral, Auto-immune, Hematological and Bacterial diseases (IMVA-HB/IDMIT), Fontenay-aux-Roses & Le Kremlin-Bicêtre, FranceBordeaux University Hopsital, Bacteriology Department, National Reference Centre for bacterial Sexually Transmitted Infections, Bordeaux, FranceBordeaux University Hopsital, Bacteriology Department, National Reference Centre for bacterial Sexually Transmitted Infections, Bordeaux, FranceBordeaux University Hopsital, Bacteriology Department, National Reference Centre for bacterial Sexually Transmitted Infections, Bordeaux, FranceDepartment of Medicine, Imperial College London, St Mary’s Campus, London, United KingdomDepartment of Medicine, Imperial College London, St Mary’s Campus, London, United KingdomUniversité Paris-Saclay, Inserm, Commissariat à l'Énergie Atomique et aux Énergies Alternatives (CEA), Center for Immunology of Viral, Auto-immune, Hematological and Bacterial diseases (IMVA-HB/IDMIT), Fontenay-aux-Roses & Le Kremlin-Bicêtre, FranceChlamydia Vaccine Research, Department of Infectious Disease Immunology, Statens Serum Institut, Copenhagen, DenmarkChlamydia Vaccine Research, Department of Infectious Disease Immunology, Statens Serum Institut, Copenhagen, DenmarkIt is of international priority to develop a vaccine against sexually transmitted Chlamydia trachomatis infections 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 with C. trachomatis SvD 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 systemic C. 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 to in vitro neutralize both SvD, SvE and SvF. Antibody responses were reflected on the vaginal and ocular mucosa, which showed detectable levels of IgG. Vaccines also induced C. trachomatis-specific cell mediated responses, as shown by in vitro stimulation 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 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.https://www.frontiersin.org/articles/10.3389/fimmu.2022.1057375/fullvaccineinfectionimmunologybacteriaCD4/CD8 lymphocytesChlamydia trachomatis |
| spellingShingle | 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 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 vaccine infection immunology bacteria CD4/CD8 lymphocytes Chlamydia trachomatis |
| title | 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 |
| title_full | 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 |
| title_fullStr | 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 |
| title_full_unstemmed | 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 |
| title_short | 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 |
| title_sort | 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 |
| topic | vaccine infection immunology bacteria CD4/CD8 lymphocytes Chlamydia trachomatis |
| url | https://www.frontiersin.org/articles/10.3389/fimmu.2022.1057375/full |
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