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A multi‐subunit Chlamydia vaccine inducing neutralizing antibodies and strong IFN‐γ + CMI responses protects against a genital infection in minipigs
Author(s) -
Bøje Sarah,
Olsen Anja Weinreich,
Erneholm Karin,
Agerholm Jørgen Steen,
Jungersen Gregers,
Andersen Peter,
Follmann Frank
Publication year - 2016
Publication title -
immunology and cell biology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.999
H-Index - 104
eISSN - 1440-1711
pISSN - 0818-9641
DOI - 10.1038/icb.2015.79
Subject(s) - virology , immunogenicity , chlamydia trachomatis , immunogen , biology , antibody , antigen , chlamydia , immunity , microbiology and biotechnology , immune system , immunology , monoclonal antibody
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 .