title: Protection against Chlamydia promoted by a subunit vaccine (CTH1) compared with a primary intranasal infection in a mouse genital challenge model.
abstract: BACKGROUND
  The chlamydial proteins CT443 (OmcB) and CT521 (rl16) have previously been identified as human B and/or T cell targets during a chlamydial infection in humans. Here we compare the protective effector mechanism promoted by a fusion protein composed of CT521 and CT443 (CTH1) with a primary intranasal Chlamydia muridarum infection known to provide high levels of protection against a genital chlamydial challenge.
  
  
  RESULTS
  The fusion protein CTH1, adjuvanted with a strong Th1 inducing cationic adjuvant (CAF01), significantly reduced the bacterial shedding compared to a control group in both a C. trachomatis Serovar D and C. muridarum challenge model. The CTH1/CAF01 vaccine was found to induce polyfunctional T cells consisting of TNFalpha/IL-2 and TNFalpha/IL-2/IFN-gamma positive cells and high titers of CTH1 specific IgG2a and IgG1. By depletion experiments the protection in the C. muridarum challenge model was demonstrated to be mediated solely by CD4(+) T cells. In comparison, an intranasal infection with C. muridarum induced a T cell response that consisted predominantly of TNFalpha/IFN-gamma co-expressing effector CD4(+) T cells and an antibody response consisting of C. muridarum specific IgG1, IgG2a but also IgA. This response was associated with a high level of protection against challenge-a protection that was only partially dependent on CD4(+) T cells. Furthermore, whereas the antibody response induced by intranasal infection was strongly reactive against the native antigens displayed in the chlamydial elementary body, only low levels of antibodies against this preparation were found after CTH1/CAF01 immunization.
  
  
  CONCLUSIONS
  Our data demonstrate that CTH1 vaccination promotes a CD4(+) T cell dependent protective response but compared with intranasal C. muridarum infection lacks a CD4 independent protective mechanism for complete protection.
authors.affiliation: Chlamydia and Adjuvant Research, Department of Infectious Disease Immunology, Statens Serum Institut, Copenhagen, Denmark. aol@ssi.dk
authors.forename: Anja Weinreich
authors.initials: AW
authors.lastname: Olsen
authors.forename: Michael
authors.initials: M
authors.lastname: Theisen
authors.forename: Dennis
authors.initials: D
authors.lastname: Christensen
authors.forename: Frank
authors.initials: F
authors.lastname: Follmann
authors.forename: Peter
authors.initials: P
authors.lastname: Andersen
mesh_terms: D000281:Administration, Intranasal; D000818:Animals; D000907:Antibodies, Bacterial / Q000276:immunology; D000918:Antibody Specificity / Q000276:immunology; D001426:Bacterial Proteins / Q000276:immunology; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology / Q000382:microbiology; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology / Q000382:microbiology; D002690:Chlamydia Infections / Q000276:immunology* / Q000382:microbiology / Q000517:prevention & control*; D023502:Chlamydia muridarum / Q000276:immunology; D016207:Cytokines / Q000096:biosynthesis; D004195:Disease Models, Animal; D004591:Electrophoresis, Polyacrylamide Gel; D005434:Flow Cytometry; D005835:Genitalia / Q000276:immunology* / Q000382:microbiology*; D006801:Humans; D007700:Kinetics; D008212:Lymphocyte Depletion; D051379:Mice; D011993:Recombinant Fusion Proteins / Q000276:immunology; D014611:Vaccination; D022223:Vaccines, Subunit / Q000276:immunology*
chemical_list: D000907:Antibodies, Bacterial; D001426:Bacterial Proteins; D016207:Cytokines; D011993:Recombinant Fusion Proteins; D022223:Vaccines, Subunit