MANIPULATING SYSTEMIC AND MUCOSAL IMMUNE-RESPONSES WITH SKIN-DELIVERABLE ADJUVANTS

Most medically important bacterial and viral pathogens gain entry into the body either via the skin or a mucosal surface. Vaccination provid es a viable and cost-effective strategy for the prevention of such dis eases and it has always been a principal aim with vaccinologists, to b e able to promote simultaneously, protective immune responses both sys temically and at mucosal surfaces. The paradigm that mucosal immunity is best stimulated by exposure to antigen via a mucosal route simply b ecause inductive sites such as Peyer's patches and bronchial associate d lymphoid tissues are located in the mucosal epithelium, has promoted a plethora of immunizing strategies aimed at delivering both antigen and adjuvant to mucosal surfaces. We have developed a novel adjuvant s ystem capable of intradermal delivery of antigens complexed in an ISCO SOME delivery vehicle. This adjuvant, referred to as a skin and mucosa l adjuvant or SAMA4, was efficacious in eliciting both systemic and mu cosal IgG and IgA antibodies in sheep, pigs and mice. SAMA4 does not i nduce granulomatous lesions at the site of vaccine delivery and can be used to deliver adjuvanted antigens by other routes including intrana sal, oral and intravaginal. Using ovalbumin as a test antigen, intrade rmally delivered ovalbumin-SAMA4 complexes was found to be very effect ive in promoting a cytotoxic T cell response. Attempts to dissect the mode of action of SAMA4 by flow cytometric analysis of lymphocyte popu lations from the spleen, lung, liver and thymus revealed an effect of route of vaccine delivery upon the composition of specific lymphocyte subsets in these various organ compartments. From this, it can be infe rred that SAMA4 induced a route-dependent re-mobilization and alterati on in lymphocyte trafficking patterns. Other mucosal adjuvants such as cholera toxin B and microspheres, when injected intradermally, tended to promote primarily, an IgG and not an IgA response against the carr ier antigen.