Induction of Protective Immunity Against Multiple STDs

$0S06FY2002GMNIH

Morehouse School Of Medicine, Atlanta GA

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Abstract

DESCRIPTION (provided by applicant): Sexually transmitted diseases (STDs) are of major medical and social importance worldwide and co-infection by more than one STD is common in high-risk populations. Genital infections caused by Chlamydia trachomatis and herpes simplex virus type 2 (HSV-2) rank among the highest STDs in the world. In fact, genital chlamydial infection is the most common bacterial STD in the United States and may cause severe irreversible complications in women, including pelvic inflammatory disease, fallopian tube scarring, ectopic pregnancy and infertility. Genital infection caused by HSV-2 is prevalent worldwide causing genital ulcerations and severe complications such as neonatal herpes and central nervous system involvement. Considering the worldwide prevalence of these STDs, vaccines offer the best approach for controlling these infections. Besides, a combination vaccine that can be administered as a single regimen to protect against multiple STDs would be highly desirable to control the rampant co-infections among STDs. Despite considerable effort, the development of an efficacious vaccine against either Chlamydia or herpes using conventional approaches has been difficult. The current paradigm for designing efficacious vaccines against these pathogens requires identification of appropriate antigens and development of effective delivery vehicles capable of eliciting high levels of Th1 response that can confer long-lasting protective immunity. The chlamydial major outer membrane protein (MOMP) and the glycoprotein D2 (gD2) of HSV-2 are highly immunogenic proteins that have been targeted as potential vaccine candidates; these proteins possess both neutralizing and T cell epitopes. We have designed a novel recombinant bacterial ghost delivery system which has inherent adjuvant properties and capable of simultaneously presenting multiple antigens to the immune system. The ultimate aim of the proposed project is to genetically design a recombinant multivalent subunit vaccine composed of Vibrio cholerae ghosts co-expressing the MOMP of C. trachomatis and the gD2 of HSV-2.

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