Vaccines for Selective Induction of Th1- and Th2-Cell Responses and Their Roles in Mucosal Immunity

Publisher Summary The site of immunization and the choice of adjuvant and vehicles to deliver vaccines all play important roles in determining the degree of dissemination of secretory IgA (S-IgA) antibodies, the predominant immunoglobulin isotype present in mucosal secretions. T-cell-mediated immune (CMI) responses are also associated with mucosal immunity and the homing of sensitized T cells appears to be similar to that described for IgA plasma cell precursors. The differentiation pathways which T-helper (Th) cells undergo during mucosal and systemic immune responses is currently receiving extensive study, since it has been suggested that the function of mature Th cells is based upon the types of cytokines produced. In particular, Th1 cells, secreting IFNγ, IL-2, and tumor necrosis factor-β (TNFβ), are associated with delayed-type hypersensitivity and are less efficient than the Th2 subset (producing IL-4, IL-5, IL-6, IL-9, IL-10, and IL-13) in providing help for antibody responses. The pattern of antibody isotypes secreted during an immune response is dependent upon the phenotype of the stimulating Th cells. Thus, in the murine system, Th1 cells through the secretion of IFNγ are more efficient in stimulating IgG2a production, whereas Th2 cells producing IL-4 induce IgGl and IgE antibodies. This chapter summarizes some of the recent findings on the role of Th1 and Th2 cells and derived cytokines for the induction and regulation of mucosal and systemic immune responses to well-defined vaccines and delivery systems. In addition it briefly discusses additional mucosal immunization approaches including mucosal delivery of soluble proteins, recombinant bacterial and viral vectors, and mucosal DNA (genetic) immunization.