ANTIGEN DELIVERY STRATEGIES FOR MUCOSAL VACCINES

Progress towards effective vaccines to control internal parasites, esp ecially those affecting mucosal compartments, has been inhibited by th e combined problems of the antigenic complexity of parasites and the l ack of understanding of the host response. However, the accumulation o f information regarding regulation of mucosal immunity has enabled a r eappraisal of vaccination options to provide appropriate mucosal effec tor responses. The pivotal role of T cell influences, and in particula r the contribution of cytokine signals, has been clearly established f rom 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 propos e a role for local Th2 cytokine production in this regard. To support this proposition, the distribution of cytokine mRNA has been determine d by in situ hybridisation techniques in normal and parasitised animal s. Further, we have shown that in the absence of Th2 cytokines (using gene knockout animals) mucosal responses are grossly deficient; we hav e also shown that this defect can be overcome by vector-directed gene therapy. These studies have indicated that new mucosal immunisation op portunities exist by combining traditional immunisation approaches wit h strategies to upregulate local cytokine production. However, the suc cess of these new strategies will depend on selection of highly immuno genic subunit antigens, coupled with techniques for cytokine manipulat ion and delivery with appropriate adjuvant/vehicle formulations. This paper reviews delivery technologies available to chaperone labile anti genic and genetic material to appropriate sites for mucosal stimulatio n after systemic or oral administration. Copyright (C) 1996 Australian Society for Parasitology. Published by Elsevier Science Ltd.