Gianni Pozzi

Commensal bacteria as vectors for mucosal vaccines against sexually transmitted diseases: vaginal colonization with recombinant streptococci induces local and systemic antibodies in mice

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.

Recombinant Streptococcus gordonii as a Live Vehicle for Vaccine Antigens

To investigate the possible use of commensal bacteria as live vehicles for vaccine antigens, we chose as a model Streptococcus gordonii, a Gram-positive coccus, which is a normal constituent of the microbial flora of the human oral cavity.1,2 The strain “Challis” of S. gordonii, formerly classified as Streptococcus sanguis? allows easy genetic manipulation because it is naturally competent for genetic transformation.4,5 S. gordonii “Challis” was also found capable of colonizing the mouse oral and vaginal mucosa (see below), thus providing an animal model for testing the immunogenicity of the recombinant strains.

Expression of Vaccine Antigens in Lactobacillus

The genus Lactobacillus comprises a remarkably diverse and heterogeneous group of Gram-positive bacilli that are ubiquitous as components of the normal indigenous flora of humans and other animals as well as being important lactic acid bacteria used for the production of and found naturally in fermented foods.1 Their “health-promoting” properties have been advocated since the early part of this century, this has resulted in their consumption in many countries as dietary adjuncts, in dairy products such as yogurts and in probiotic preparations.2–5 Administration of viable Lactobacillus strains has been described as therapeutic for diarrhea and other intestinal disorders, vaginitis and urinary tract infections. The mechanisms underlying this effect are not well understood, although they probably involve restoration of the natural balance between the normal microflora and the invading organism, which in turn results in elimination of the pathogen by the hosts’ immune system. Lactobacilli are rarely pathogenic, thus making them an excellent choice for consideration as vaccine delivery vehicles.