A multi-subunit Chlamydia vaccine inducing neutralizing antibodies and strong IFN-γ⁺ CMI responses protects against a genital infection in minipigs.
Chlamydia is the most widespread sexually transmitted bacterial disease and a prophylactic vaccine is highly needed. Ideally, this vaccine is required to induce a combined response of Th1 cell-mediated immune (CMI) response in concert with neutralizing antibodies. Using a novel Göttingen minipig animal model, we evaluated the immunogenicity and efficacy of a multi-subunit vaccine formulated in the strong Th1-inducing adjuvant CAF01. We evaluated a mixture of two fusion proteins (Hirep1 and CTH93) designed to promote either neutralizing antibodies or cell-mediated immunity, respectively. Hirep1 is a novel immunogen based on the variant domain (VD) 4 region from major outer membrane protein (MOMP) serovar (Sv) D, SvE and SvF, and CTH93 is a fusion molecule of three antigens (CT043, CT414 and MOMP). Pigs were immunized twice intramuscularly with either Hirep1+CTH93/CAF01, UV-inactivated Chlamydia trachomatis SvD bacteria (UV-SvD/CAF01) or CAF01. The Hirep1+CTH93/CAF01 vaccine induced a strong CMI response against the vaccine antigens and high titers of antibodies, particularly against the VD4 region of MOMP. Sera from Hirep1+CTH93/CAF01 immunized pigs neutralized C. trachomatis SvD and SvF infectivity in vitro. Both Hirep1+CTH93/CAF01 and UV-SvD/CAF01 vaccination protected pigs against a vaginal C. trachomatis SvD infection. In conclusion, the Hirep1+CTH93/CAF01 vaccine proved highly immunogenic and equally protective as UV-SvD/CAF01 showing promise for the development of a subunit vaccine against Chlamydia.
Section of Veterinary Reproduction and Obstetrics, Department of Large Animal Sciences, Faculty of Health and Medical Sciences, University of Copenhagen, Frederiksberg C, Denmark.|Chlamydia Vaccine Research, Department of Infectious Disease Immunology, Statens Serum Institut, Copenhagen S, Denmark.
Sarah
S
Bøje
Chlamydia Vaccine Research, Department of Infectious Disease Immunology, Statens Serum Institut, Copenhagen S, Denmark.
Anja Weinreich
AW
Olsen
Section of Veterinary Reproduction and Obstetrics, Department of Large Animal Sciences, Faculty of Health and Medical Sciences, University of Copenhagen, Frederiksberg C, Denmark.|Chlamydia Vaccine Research, Department of Infectious Disease Immunology, Statens Serum Institut, Copenhagen S, Denmark.
Karin
K
Erneholm
Section of Veterinary Reproduction and Obstetrics, Department of Large Animal Sciences, Faculty of Health and Medical Sciences, University of Copenhagen, Frederiksberg C, Denmark.
Jørgen Steen
JS
Agerholm
Immunology and Vaccinology, National Veterinary Institute, Technical University of Denmark, Frederiksberg C, Denmark.
Gregers
G
Jungersen
Chlamydia Vaccine Research, Department of Infectious Disease Immunology, Statens Serum Institut, Copenhagen S, Denmark.
Peter
P
Andersen
Chlamydia Vaccine Research, Department of Infectious Disease Immunology, Statens Serum Institut, Copenhagen S, Denmark.
Frank
F
Follmann
D000818:Animals; D057134:Antibodies, Neutralizing / Q000097:blood; D001425:Bacterial Outer Membrane Proteins / Q000008:administration & dosage / Q000235:genetics / Q000276:immunology*; D001428:Bacterial Vaccines / Q000008:administration & dosage / Q000235:genetics / Q000276:immunology*; D002689:Chlamydia / Q000276:immunology*; D002690:Chlamydia Infections / Q000517:prevention & control*; D004195:Disease Models, Animal; D006801:Humans; D007111:Immunity, Cellular; D007114:Immunization; D007371:Interferon-gamma / Q000276:immunology; D011993:Recombinant Fusion Proteins / Q000008:administration & dosage / Q000235:genetics / Q000276:immunology; D013552:Swine; D013556:Swine, Miniature; D018417:Th1 Cells / Q000276:immunology*; D015164:Vaccines, Inactivated / Q000008:administration & dosage / Q000235:genetics / Q000276:immunology; D022223:Vaccines, Subunit / Q000008:administration & dosage / Q000235:genetics / Q000276:immunology
D057134:Antibodies, Neutralizing; D001425:Bacterial Outer Membrane Proteins; D001428:Bacterial Vaccines; D011993:Recombinant Fusion Proteins; D015164:Vaccines, Inactivated; D022223:Vaccines, Subunit; C101031:major outer membrane protein, Chlamydia pneumoniae; D007371:Interferon-gamma