VAGINAL IMMUNIZATION WITH RECOMBINANT GRAM-POSITIVE BACTERIA

PROBLEM: Many viral and bacterial pathogens enter the body through the genital mucosa. Therefore, one of the major goals of a vaccine agains t sexually transmitted diseases (STDs) should be to induce an immune r esponse in the genital mucosa capable of controlling the entry of the pathogen. Our approach for the development of vaccines against STDs is based on the use of nonpathogenic Gram-positive bacteria as live vacc ine vectors. METHOD OF STUDY: Recombinant Gram-positive bacteria expre ssing vaccine antigens were constructed using genetic systems develope d in our laboratory. Balb/c mice and Cynomolgus monkeys were inoculate d by the vaginal route and vaginal samples were collected using absorb ent wicks. Colonization was evaluated by the presence of recombinant b acteria in the vaginal samples. Local and systemic immune responses we re studied. RESULTS: We have developed genetic systems for the express ion of heterologous antigens on the surface of the human commensals St reptococcus gordonii and Lactobacillus spp. Both S. gordonii and L. ca sei stably colonized the murine vagina after a single inoculum. Vagina l colonization of mice with recombinant strains of S. gordonii, expres sing human papillomavirus (HPV) and human immunodeficiency virus (HIV) antigens, induced antigen-specific vaginal immunoglobulin A (IgA) and serum IgG. Local and systemic immune responses also were detected in monkeys immunized intravaginally with recombinant S. gordonii. CONCLUS ION: The results obtained indicated that the approach of using coloniz ing Gram-positive bacteria as live vectors has a great potential for t he development of vaccines against STDs.