Antigen delivery strategies for mucosal vaccines

Progress towards effective vaccines to control internal parasites, especially those affecting mucosal compartments, has been inhibited by the combined problems of the antigenic complexity of parasites and the lack of understanding of the host response. However, the accumulation of information regarding regulation of mucosal immunity has enabled a reappraisal of vaccination options to provide appropriate mucosal effector responses. The pivotal role of T cell influences, and in particular the contribution of cytokine signals, has been clearly established from in vitro studies, but data emerging from our laboratories provide evidence for these effects in vivo. We have demonstrated the role of T cells in determining the outcome of an intestinal response and propose a role for local Th2 cytokine production in this regard. To support this proposition, the distribution of cytokine mRNA has been determined by in situ hybridisation techniques in normal and parasitised animals. Further, we have shown that in the absence of Th2 cytokines (using gene knockout animals) mucosal responses are grossly deficient; we have also shown that this defect can be overcome by vector-directed gene therapy. These studies have indicated that new mucosal immunisation opportunities exist by combining traditional immunisation approaches with strategies to upregulate local cytokine production. However, the success of these new strategies will depend on selection of highly immunogenic subunit antigens, coupled with techniques for cytokine manipulation and delivery with appropriate adjuvant/vehicle formulations. This paper reviews delivery technologies available to chaperone labile antigenic and genetic material to appropriate sites for mucosal stimulation after systemic or oral administration.