Recombinant Multivalent Subunit Combination Vaccine Against Multiple STDs

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Sexually transmitted diseases (STDs) are of major medical and social importance worldwide, affecting about 500 million people annually, with debilitating or life-threatening consequences. Genital infections caused by Chlamydia trachomatis and Herpes simplex virus type 2 (HSV-2) rank among the highest STDs in the world. Genital chlamydial infection is the most common bacterial STD in the United States with severe irreversible complications in women, including pelvic inflammatory disease, fallopian tube scarring, ectopic pregnancy and infertility. Four million reported annual cases involve over $2 billion in treatment cost. Genital herpes is a widespread STD with severe complications, especially in neonates and immunocompromised individuals, including neonatal herpes and central nervous system involvement. Of the current control and prevention strategies, including early detection and treatment, vaccines capable of protecting against infection or severe disease would be the most effective long-term option to control diseases due to Chlamydia and HSV-2. A vaccine offers the best approach to protect the greatest number of people against infection. There is currently no licensed vaccine against either Chlamydia or herpes infections. Considering the high incidence of coinfections by both C. trachomatis and HSV-2, the availability of a combination vaccine that can be administered as a single regimen to protect against multiple infections would be highly desirable. Efficacious vaccines against Chlamydia and genital herpes would require identification of appropriate antigens and development of effective delivery vehicles capable of eliciting long-lasting protective immunity. We have designed a novel recombinant bacterial ghost delivery system which has inherent adjuvant properties and capable of simultaneously delivering multiple antigens from the same or different pathogens to the immune system. This proposal describes the use of the novel recombinant Vibrio cholerae ghost (rVCG) technology to develop a multivalent subunit combination vaccine comprising select outer membrane proteins (OMPs) including the highly immunogenic major OMP (MOMP) and PorB of C. trachomatis and the glycoprotein D (gD2) and B (gB2) of HSV-2. The hypothesis to be investigated is that immunization with a multivalent combination vaccine composed of rVCG expressing subunit antigens from both Chlamydia and HSV- 2 will simultaneously induce protective immunity against both genital Chlamydia and herpes infections. We have chosen MOMP, PorB, gD2 and gB2 as appropriate immunogens since these antigens contain protective T cell and neutralizing epitopes. Our aims are to: (a) genetically design an rVCG vectorbased multivalent subunit combination vaccine, and (b) assess the immunogenicity and protective efficacy of this vaccine construct in an appropriate animal model. Results from these studies will likely lead to the development of a reliable combination vaccine regimen against Chlamydia and HSV-2, which should have major implications for the control of STDs and their complications.