PROSPECTS FOR ORAL VACCINATION USING RECOMBINANT BACTERIA EXPRESSING VIRAL EPITOPES

Live attenuated bacteria are attractive carriers for foreign antigens by the oral route. Salmonella can be attenuated by genetic manipulations so that they are nonpathogenic, but retain the ability to invade across the gut epithelium and persist in the gut-associated lymphoid tissue (GALT), in Peyer's patches and in the spleen, where they can deliver foreign antigens to the host immune system. The development of genetically defined attenuated strains converges with the power of recombinant gene expression technology, which is most advanced in prokaryotes, such as Escherichia coli and Salmonella typhimurium. In theory, every foreign antigen could be transported to defined compartments of the host immune system, using attenuated Salmonella or other attenuated bacteria that are less well studied as carriers. In addition to the systemic immune responses, immune responses can be generated at mucosal surfaces that are inaccessible to normal parenteral immunization schedules. The gut- and the bronchius-associated lymphoid tissues constitute the main part of an immunological system common to all mucosal surfaces: the mucosal-associated lymphoid tissue (MALT). The delivery of antigens by the oral route to the GALT leads to a generalized mucosal immune response, of which the secretory IgA component is the best studied. Dependent on whether the systemic immune responses and/or mucosal immunity are required, bacteria attenuated to varying degrees of invasiveness or bacteria that are restricted to the epithelial layers could be considered as carriers for viral antigens. This chapter describes the current experimental situation, using mainly the attenuated Salmonella strains to immunize against viral antigens, and some major obstacles and considerations relevant to recombinant live oral antiviral vaccines based on bacteria. © 1992, Academic Press Inc.