The objective of this project is the development of subunit or recombinant vaccine to prevent infections caused by Chlamydia trachomatis. Chlamydiae are a major cause of sexually transmitted diseases (STDs) and trachoma which remains the worlds leading cause Of preventable blindness. A vaccine capable of preventing chlamydial infection or reducing chlamydial disease sequelae is badly needed. Chlamydial infections are restricted to the oculogenital mucosae and are caused by multiple chlamydial serovars. Local antibody (sIgA) plays an important role in protection against chlamydial colonization and infection of mucosal epithelial cells. The goal of this work is to generate a subunit or recombinant chlamydial vaccine capable of evoking broadly cross-protective anti-chlamydial neutralizing at the oculagenital mucosae. Towards this end we have identified key T-helper and B-cell neutralizing epitopes of the chlamydial major outer membrane protein (MOMP); the principle neutralizing antigen of chlamydiae. Several approaches are being used to target these key MOMP antigenic determinants to evoke a mucosal immune response. These include incorporation of the epitopes as chemical and gene fusions with the B subunit of cholera toxin and the construction of recombinant polioviruses expressing MOMP epitopes as gene fusions with the poliovirus major capsid protein VP1. Our most promising results have been with recombinant poliovirus vectors. Recombinant poliovirus expressing antigenically common MOMP neutralizing epitopes grew nearly as well as parent virus and were highly immunogenic in rabbits evoking high titered serum anti- chlamydial antibodies that were broadly cross neutralizing in vitro. Future work will involve evaluating the protective efficacy of the poliovirus/MOMP chimeric virus in a non-human primate animal model of C. trachomatis ocular and genital tract infection.
