Use of novel adjuvants and delivery systems to improve the humoral and cellular immune response to malaria vaccine candidate antigens.

The immune effector mechanisms responsible for the solid protection against malaria, as demonstrated by immunization with radiation-attenuated sporozoites, are poorly understood. An effective malaria vaccine must induce a well orchestrated combination of humoral and cellular immune responses directed against critical parasite antigens/epitopes expressed during different stages of the parasite's complicated life cycle. Currently licensed human vaccine adjuvants, such as alum, may improve antibody production but are poor stimulators of cellular effector mechanisms, while potent cellular stimulants such as Freund's adjuvant are too reactogenic for human use. Over the last 5 years we have systematically evaluated several methods of antigen presentation to include chemical conjugation to bacterial carrier proteins, emulsification in 'Freund's-like' preparations, and incorporation into liposomes. This work has resulted in the production of safe, potent vaccine delivery systems capable of targeting multiple antigenic determinants to the host's immune system. Further advances in malaria vaccine development now depend on the identification of appropriate parasite epitopes for inclusion in a multicomponent-multistage vaccine.