Vaccination strategies for mucosal immune responses

Mucosal administration of vaccines is an important approach to the inductio n of appropriate immune responses to microbial and other environmental anti gens in systemic sites and peripheral blood as well as in most external muc osal surfaces. The development of specific antibody- or T-cell-mediated imm unologic responses and the induction of mucosally induced systemic immunolo gic hyporesponsiveness (oral or mucosal tolerance) depend on complex sets o f immunologic events, including the nature of the antigenic stimulation of specialized lymphoid structures in the host, antigen-induced activation of different populations of regulatory T cells (Th1 versus Th2), and the expre ssion of proinflammatory and immunoregulatory cytokines. Availability of mu cosal vaccines will provide a painless approach to deliver large numbers of vaccine antigens for human immunization. Currently, an average infant will receive 20 to 25 percutaneous injections for vaccination against different childhood infections by 18 months of age. It should be possible to develop for human use effective, nonliving, recombinant, replicating, transgenic, and microbial vector- or plant-based mucosal vaccines to prevent infections . Based on the experience with many dietary antigens, it is also possible t o manipulate the mucosal immune system to induce systemic tolerance against environmental, dietary, and possibly other autoantigens associated with al lergic and autoimmune disorders. Mucosal immunity offers new strategies to induce protective immune responses against a variety of infectious agents. Such immunization may also provide new prophylactic or therapeutic avenues in the control of autoimmune diseases in humans.