Soluble or sub-unit
protein vaccines alone are incapable of generating
antigen-specific cellular immune responses. This failure can be attributed to the manner in which the immune system processes
antigen; endogenous
antigens are cycled through the MHC class I pathway to stimulate CD8+ restricted responses and exogenous
antigens are processed through the MHC class II pathway to generate humoral immunity. Traditionally sub-unit
vaccines have been formulated with adjuvants to enhance immunogenicity, however in the last decade a number of adjuvants have been developed that effectively stimulate the generation of both humoral and cellular immune responses, although the manner in which they exert their effects has not been investigated. Here we describe
Tomatine, a glycoalkaloid based adjuvant, capable of stimulating potent
antigen-specific humoral and cellular immune responses that contribute to protection against
malaria, Francisella tularensis and regression of experimental
tumors. Using in vivo models we investigated the manner in which cellular immune responses were generated by
Tomatine. We established that
Tomatine did not require either lymph node or splenic macrophages to generate cytotoxic T lymphocytes (CTL) and delivered soluble
protein into a pathway not dependant on the machinery of the classical MHC class I pathway. We also observed that at the molecular level
Tomatine required both CD80 and CD86 costimulation to engender
antigen-specific cellular immunity.