A Multi-Subunit Chlamydia Vaccine Inducing Neutralizing Antibodies and Strong IFN-γ⁺ CMI Responses Protects Against a Genital Infection in Minipigs

Immunol Cell Biol. 2016 Feb;94(2):185-95. doi: 10.1038/icb.2015.79. Epub 2015 Aug 13.

Abstract

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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Antibodies, Neutralizing / blood
  • Bacterial Outer Membrane Proteins / administration & dosage
  • Bacterial Outer Membrane Proteins / genetics
  • Bacterial Outer Membrane Proteins / immunology*
  • Bacterial Vaccines / administration & dosage
  • Bacterial Vaccines / genetics
  • Bacterial Vaccines / immunology*
  • Chlamydia / immunology*
  • Chlamydia Infections / prevention & control*
  • Disease Models, Animal
  • Humans
  • Immunity, Cellular
  • Immunization
  • Interferon-gamma / immunology
  • Recombinant Fusion Proteins / administration & dosage
  • Recombinant Fusion Proteins / genetics
  • Recombinant Fusion Proteins / immunology
  • Swine
  • Swine, Miniature
  • Th1 Cells / immunology*
  • Vaccines, Inactivated / administration & dosage
  • Vaccines, Inactivated / genetics
  • Vaccines, Inactivated / immunology
  • Vaccines, Subunit / administration & dosage
  • Vaccines, Subunit / genetics
  • Vaccines, Subunit / immunology

Substances

  • Antibodies, Neutralizing
  • Bacterial Outer Membrane Proteins
  • Bacterial Vaccines
  • Recombinant Fusion Proteins
  • Vaccines, Inactivated
  • Vaccines, Subunit
  • major outer membrane protein, Chlamydia pneumoniae
  • Interferon-gamma