Chlamydia trachomatis is the most prevalent sexually transmitted pathogen in the United States and causes numerous genitourinary diseases including PID and infertility. C.trachomatis is also a major cause of infant conjunctivitis and pneumonia. Ocular infection caused by C.trachomatis are the leading cause of preventable blindness in the developing world. Most subunit vaccine studies have employed the C.trachomatis major outer membrane protein, or peptides derived from it, as an immunogen with only modest success. The identification of alternate surface proteins to test as subunit vaccine candidates could significantly hasten the development of an effective anti-Chlamydial vaccine. Using adhesin technology, MicroCarb has identified two apparently surface-localized Chlamydial adhesin proteins; and approximately80Kdal protein, which binds to the glycolipid gangliotetraosylceramide (asialo-GM1) and about-140 Kdal protein that binds to heparin sulfate.
The specific aims of this proposal are: 1) further characterize the - 140Kdal heparin-binding protein; 2) establish the distribution and expression pattern for the -140Kdal adhesin protein among clinically relevant C.trachomatis serovars by both genetic and serological means; 3) produce sufficient quantities of recombinant -140 Kdal adhesin for preclinical testing; and 4) determine immunogenicity and protective ability of recombinant adhesin using the mouse genital infectivity model systems.
A recombinant heparin-binding surface adhesin from C.trachomatis will be evaluated as a subunit vaccine using appropriate animal model systems. If this subunit is found to protect animals against intravaginal challenge with homologous and heterologous C.trachomatis serovars, the subunit will be placed in clinical trials for evaluation as a human vaccine to prevent sexually transmitted disease and trachoma.
