The overall goal of this project is to develop a recombinant or synthetic vaccine for the prevention and/or control of Chlamydia trachomatis infections of humans. The chlamydial diseases for which a vaccine is needed are blinding trachoma and salpingitis. We have previously shown that the immune response to chlamydial infection stimulates both protective and immunopathogenic responses. The antigens that elicit these responses are distinct. These immunologically relevant antigens have been identified and characterized. The protective immune response is mediated by local secretory antibody and is directed against serotype-specific antigenic epitopes located on the major outer membrane protein (MOMP). The deleterious immune response is cell mediated and is directed towards a conformational genus-specific determinant located on a 57K outer membrane protein. The current strategy of this laboratory is to generate recombinant or synthetic immunogens composed of the protective serotype-specific MOMP determinants and test these as vaccine candidates. To this, end, the MOMP genes from four C trachomatis serovars have been cloned, sequenced, and epitope mapped using lambda gtll subclones expressing antigenic determinants reactive with protective MOMP monoclonal antibodies. These mapping studies have identified both the immunodominant B cell MOMP epitope and a closely associated highly conserved alpha-helical amphipathic sequence that may be the immunoregulatory T-helper cell determinant. Those regions that encode for the T-helper cell and B cell MOMP determinants will be subcloned into expression vectors, and the recombinant antigens isolated and used as vaccine candidates in chlamydial animal models. Two approaches will be followed for the development of a chlamydial vaccine using recombinant antigen: (1) to prime the host immune response with protective recombinant antigens with experimental or natural exposure providing the antigenic stimulus for induction of a protective secondary immune response, or (ii) to employ recombinant antigen to selectively boost protective immunity in animals previously primed by experimental infection.
