Development of the Recombinant Vaccines with Lactic Acid Bacteria as Antigens Delivery Vehicles for Mucosal Immunization

Abstract

Recently, a great deal of attention has focused on mucosal immunization. Oral or mucosal immunization wiil be important as a means of inducing secretory IgA antibodies directed against specific pathogens of mucosal surfaces. Despite great interest in mucosal immunization, the success of mucosal immunizations has been very limited. Recently, component vaccine strategies have become popular for the development of new vaccines, and there have been reports of several excellent antigens delivery systems suitable for mucosal administration. One such system is a live attenuated cell invasible bacterium that expresses protective antigens of unrelated microorganisms, and the second is chemically synthesized microparticles, which are conjugated with antigenic epitopes. Live attenuated vectors have to be converted into nonpathogenic systems that are still capable of inducing protective immunity. However, it is difficult to evaluate the safety of these vectors. From this point of view, the chemically synthesized microparticles are more useful. This system requires the purification of antigens prior to particle formation, which may be time consuming and expensive. Our research has been directed toward developing carrier systems using nonpathogenic bacteria. Lactic acid bacteria have a long history of use in food fermentation, and therefore are classified: “generally regarded as safe.” They are able to survive or grow in the gastrointestinal tract of humans and animals. Lactococcus lactis, for which various genetic modification systems are available, is thought to be potentially useful for the production of heterologous peptides and proteins in foods and medicines, but for use in vaccination, this bacterium needs some modifications, because it does not invade nor colonise the mucosal surfaces, nor does it evoke strong immune responses to itself. In this report, I will summarize the present studies about developing mucosal vaccines against enteric pathogens, and discuss the potential for development of the recombinant vaccines with lactic acid bacteria as antigens delivery vehicles for mucosal immunization.