Development of epitope-based CD8 alpha beta CTL vaccines requires effective strategies for codelivery of large numbers of individual epitopes. We have designed an artificial "polyepitope" protein containing 10 contiguous minimal CTL epitopes, which were restricted by five MHC alleles and derived from five viruses, a parasite, and a tumor model. A recombinant vaccinia virus coding for this protein was capable of inducing MHC-restricted primary CTL responses to all 10 epitopes. Mice immunized with this recombinant vaccinia showed protection against murine cytomegalovirus, Sendai virus, and a tumor model. This simple generic approach to multiepitope delivery should find application in CTL-based vaccine design.