NEUTRALIZABLE EPITOPES OF CHLAMYDIA TRACHOMATIS

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The overall goal of this proposal is to determine whether peptides corresponding to neutralizable contiguous epitopes of the major outer membrane protein (MOMP) of Chlamydia trachomatis are able to confer protection from an infection with this organism. This pathogen is the leading cause of sexually transmitted disease in the Western world and has been implicated as a major contributing factor to infertility. It is also the leading cause of preventable blindness in underdeveloped countries. Due to the morbidity associated with this organism, attempts have been made to vaccinate with the intact organism. From vaccine trials it was concluded that the host immune response contributed to the damaging sequelae associated with a chlamydial infection. More recently in an effort to both circumvent the hypersensitivity reaction as well as increase the number of serovars represented in a vaccine, subunit vaccines have been proposed as a possible solution. Although we realize that both protective B and T cell epitopes will eventually need to be incorporated into an effective vaccine, in this proposal we will focus on epitopes that we have identified and characterized as contiguous and neutralizable to determine whether peptides representing these epitopes can afford protection to the host. We will first focus on serovar E since it is the most common genital isolate of C. trachomatis. Peptides representing neutralizable epitopes will be tested alone, in combination and as a colinear peptide construct for their ability to elicit a protective immune response. The colinear peptides will be used to establish the optimal peptide construction, immunization route, dose, delivery system and if necessary, adjuvant that will elicit a strong mucosal response. Paralleling these efforts we will be working with a murine model of a chlamydial genital infection in order to establish a reproducible model that will be suitable for testing the ability of the immunization parameters established with the peptide constructs to protect or attenuate from a chlamydial infection and the sequelae of infertility. Information gained from this approach should bring us closer to answering the question as to the role of neutralizing antibodies in chlamydial infections.