There is a need to develop vaccines to control the spread of sexually transmitted diseases (STDs). Novel immunization strategies that elicit a mucosal immune response in the genital tract, may show improved protection by preventing or at least limiting entry of the pathogenic micro-organism. However, it has proven difficult to obtain a local immune response in the vaginal mucosa. Our approach is based on the use of recombinant bacteria capable of colonizing mucosal surfaces as live vaccine vectors. The human commensal Streptococcus gordonii, engineered to express the E7 protein of human papillomavirus type 16, was used for intravaginal immunization of mice. A single inoculum of recombinant bacteria was sufficient to establish colonization of the murine vagina and therefore induce papillomavirus-specific vaginal IgA and serum IgG. Evidence that mucosal colonization with recombinant commensal bacteria can induce a local immune response in the female genital tract represents a significant step toward the development of new vaccines against STDs.