Chlamydial trachomatis is a leading cause of sexually transmitted diseases worldwide for which there is no effective vaccine. The objective of this project is the design of recombinant vaccines for the prevention of infections caused by Chlamydia trachomatis. Chlamydial infections are restricted to the oculogenital mucosae and are caused by multiple chlamydial serovars. Local antibody (sIgA) is thought to play 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 IgA antibodies at the oculogenital mucosae. The chlamydial major outer membrane protein (MOMP) is the principle neutralizing antigen on the chlamydial surface. Several approaches are being used to target rMOMP or protective MOMP epitopes to evoke sIgA anti-chlamydial neutralizing antibodies. These include incorporation of the epitopes as gene fusions with the B subunit of E. coli enterotoxin (LT), the construction of recombinant polioviruses expressing MOMP epitopes as gene fusions with the poliovirus major capsid protein VP1, and encapsulation of MOMP into microspheres. Our findings show that each of these approaches is capable of eliciting high titered serum anti-chlamydial neutralizing antibodies (IgG) following parenteral immunization however none of these systems has been effective in evoking local sIgA responses. Future studies will focus on the generation of recombinant LT-MOMP immunogens designed to both optimize the mucosal adjuvanticity of LT and the mucosal immune response against the MOMP.
