The immediate goals of this project are to define and molecularly characterize chlamydial surface components that are virulence determinants or antigens of importance in the hosts immune response to chlamydial infection. The long-term objectives are to: (i) understand how chlamydiae interact with and infect eukaryotic cells, (ii) define pathogenetic mechanisms of chlamydial disease, (iii) identify target antigens for development of a recombinant vaccine to prevent and/or control chlamydial diseases in humans. We have previously shown that the immune response to chlamydial infection has both protective and deleterious components. The antigens associated with these responses are distinct. The protective antigen is the major outer membrane protein (MOMP) and the deleterious antigen is a 57-kDa protein. The MOMP genes from several C. trachomatis serovars have been cloned and sequenced. Serotype, serogroup, and species-specific epitopes have been located on MOMP with a panel of protective monoclonal antibodies (MAbs). Sequence analysis showed the MOMP genes encode proteins with highly conserved regions interrupted symmetrically by four short variable domains (VD). The VDs possess contiguous antigenic determinants recognized by protective MAbs. Surface proteolysis of intact chlamydiae with trypsin selectively cleaves within these VDs and abolishes attachment of chlamydiae to HeLa cells. These findings implicate MOMP as a chlamydial adhesion and suggest that the contiguous sequences within these VDs are potential vaccine candidate antigens. Current studies are directed at identification of MOMP T-cell determinants and the construction of live enteric vaccine vectors expressing co-line protective MOMP B-cell determinants and the construction of live enteric vaccine vectors expressing co-linear protective MOMP B-cell determinants and T- helper cell determinants as antigenic hybrid proteins. Protective MOMP sequences are being cloned and expressed as antigenic hybrids of the LamB protein in S. typhimurium and VP1 of the Sabin type 1 vaccine strain. The immunogenicity and vaccine efficacy of these infectious recombinant vectors is currently being evaluated.
