A multi-subunit Chlamydia vaccine inducing neutralizing antibodies and strong IFN-γ⁺ CMI responses protects against a genital infection in minipigs

TY - JOUR

T1 - A multi-subunit Chlamydia vaccine inducing neutralizing antibodies and strong IFN-γ⁺ CMI responses protects against a genital infection in minipigs

AU - Bøje, Sarah Henriette

AU - Olsen, Anja Weinreich

AU - Erneholm, Karin Susanne

AU - Agerholm, Jørgen Steen

AU - Jungersen, Gregers

AU - Andersen, Peter

AU - Follmann, Frank

PY - 2016/2/1

Y1 - 2016/2/1

N2 - 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.

AB - 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.

KW - Animals

KW - Antibodies, Neutralizing

KW - Bacterial Outer Membrane Proteins

KW - Bacterial Vaccines

KW - Chlamydia

KW - Chlamydia Infections

KW - Disease Models, Animal

KW - Humans

KW - Immunity, Cellular

KW - Immunization

KW - Interferon-gamma

KW - Recombinant Fusion Proteins

KW - Swine

KW - Swine, Miniature

KW - Th1 Cells

KW - Vaccines, Inactivated

KW - Vaccines, Subunit

KW - Journal Article

KW - Research Support, Non-U.S. Gov't

U2 - 10.1038/icb.2015.79

DO - 10.1038/icb.2015.79

M3 - Journal article

C2 - 26268662

SN - 0818-9641

VL - 94

SP - 185

EP - 195

JO - Immunology and Cell Biology

JF - Immunology and Cell Biology

IS - 2

ER -