A CHLAMYDIAL MAJOR OUTER-MEMBRANE PROTEIN EXTRACT AS A TRACHOMA VACCINE CANDIDATE

Purpose. As shown in infected humans and iri animal models of chlamydi al infection, the major outer membrane protein (MOMP) of Chlamydia tra chomatis is immunogenically potent. The purpose of this investigation was to test in the cynomolgus monkey model of trachoma a new extract o f MOMP as a candidate vaccine against ocular chlamydial infection. Met hod. The nonionic detergent octyl-beta-D glucopyranoside (OGP) was use d to extract MOMP from purified C. trachomatis (serovar C) elementary bodies. Protective immunization with OGP-MOMP by mucosal and systemic routes was compared in the cynomolgus monkey model of trachoma. All co ntrol and immunized monkeys were challenged by topical application of infectious C. trachomatis to the conjunctivae 35 days after the initia tion of immunization. Results. Immunization with OGP-extracted MOMP su ccessfully induced chlamydia-specific local and systemic immunity to M OMP and to whole organism before challenge and early clearance of infe ction by systemically immunized monkeys. Although ocular disease was n ot significantly reduced in either immunized group compared to control animals, the lowest clinical and microbiologic disease scores develop ed in two animals in the mucosal group with the highest immunoglobulin A tear antibody titers at days 0 to 14, whereas higher tear and serum immunoglobulin G correlated with reduced disease in the systemically immunized group.Conclusions. These data demonstrate that despite evide nce of vigorous MOMP-specific and other chlamydia-specific serologic a nd cell-mediated immunity, as well as anamnestic serologic responses t o chlamydia, vaccination with OGP-MOMP was only partially protective a gainst chlamydial ocular disease. The partial protection correlated be st with tear immunoglobulin A responses after mucosal immunization and with local and systemic immunoglobulin G responses after peripheral i mmunization, suggesting that alternative chlamydial antigens may have td be considered in future vaccine development to induce more effectiv e protective immunity and that evaluation of efficacy must be appropri ate to route of immunization.