RECOMBINANT POLYEPITOPE VACCINES FOR THE DELIVERY OF MULTIPLE CD8 CYTOTOXIC T-CELL EPITOPES

Development of epitope-based CD8 alpha beta CTL vaccines requires effe ctive strategies for codelivery of large numbers of individual epitope s. We have designed an artificial ''polyepitope'' protein containing 1 0 contiguous minimal CTL epitopes, which were restricted by five MHC a lleles and derived from five viruses, a parasite, and a tumor model. A recombinant vaccinia virus coding for this protein was capable of ind ucing MHC-restricted primary CTL responses to all 10 epitopes. Mice im munized with this recombinant vaccinia showed protection against murin e cytomegalovirus, Sendai virus, and a tumor model. This simple generi c approach to multiepitope delivery should find application in CTL-bas ed vaccine design.