A chlamydial major outer membrane protein extract as a trachoma vaccine candidate.

This content is PDF only. Please click on the PDF icon to access.

Abstract

PURPOSE: As shown in infected humans and in animal models of chlamydial infection, the major outer membrane protein (MOMP) of Chlamydia trachomatis is immunogenically potent. The purpose of this investigation was to test in the cynomolgus monkey model of trachoma a new extract of MOMP as a candidate vaccine against ocular chlamydial infection. METHOD: The nonionic detergent octyl-beta-D glucopyranoside (OGP) was used 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 control and immunized monkeys were challenged by topical application of infectious C. trachomatis to the conjunctivae 35 days after the initiation of immunization. RESULTS: Immunization with OGP-extracted MOMP successfully induced chlamydia-specific local and systemic immunity to MOMP and to whole organism before challenge and early clearance of infection by systemically immunized monkeys. Although ocular disease was not significantly reduced in either immunized group compared to control animals, the lowest clinical and microbiologic disease scores developed in two animals in the mucosal group with the highest immunoglobulin A tear antibody titers at day 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 evidence of vigorous MOMP-specific and other chlamydia-specific serologic and cell-mediated immunity, as well as anamnestic serologic responses to chlamydia, vaccination with OGP-MOMP was only partially protective against chlamydial ocular disease. The partial protection correlated best with tear immunoglobulin A responses after mucosal immunization and with local and systemic immunoglobulin G responses after peripheral immunization, suggesting that alternative chlamydial antigens may have to be considered in future vaccine development to induce more effective protective immunity and that evaluation of efficacy must be appropriate to route of immunization.