Ocular chlamydial infections were studied in cynomolgus monkeys in order to evaluate the role of surface antigens in (1) resistance to reinfection and (ii) immunopathogenesis of disease. (i) Resistance to reinfection. Cynomolgus monkeys (Macaca fasicularis) were infected with a C. trachomatis trachoma biovar producing an acute follicular conjunctivitis. The temporal appearance of tear and serum antibodies reactive with C. trachomatic surface antigens were determined by immunoblotting analysis and radioimmunoprecipitation during this self-limiting disease. The chlamydial major outer membrane protein (MOMOP) was found to be the primary immunogen recognized by monkey tear IgA antibodies during infection. The tear IgA antibody MOMP response was specific for the infecting trachoma serovar suggesting that antibodies directed against antigenically unique portions of the MOMP were protective. Monoclonal antibodies were generated against the MOMP that recognized antigenically unique epitopes and were found to neutralize the in vivo toxicity of the organism for mice and infectivity for the monkey eye. Purified native MOMP and recombinant MOMP are currently being tested as a subunit vaccine in the monkey model. (ii) Immunopathogenesis of disease. When administered onto the conjunctivae of immune but not naive monkeys, a Triton X-100 extract of chlamydiae produced an inflammatory response indistinguishable from that observed in monkeys with primary chlamydial conjunctivitis. This inflammatory response was not due to chlamydial infection and was characteristic of a delayed-type hypersensitivity reaction. The antigenic fraction that induced this deleterious immune response did not contain the protective MOMP antigen. Studies are currently underway aimed at characterization of this antigen. Preliminary results show that the deleterious antigen is heat labile and common to the genus chlamydiae. The significance of this project lies in the understanding of the pathogenesis of chlamydial diseases and in the development of a subunit chlamydial vaccine.
