DELIVERY OF MULTIPLE CD8 CYTOTOXIC T-CELL EPITOPES BY DNA VACCINATION

Development of CD8 alpha beta CTL epitope-based vaccines requires an e ffective strategy capable of co-delivering large numbers of CTL epitop es, Here we describe a DNA plasmid encoding a polyepitope or ''polytop e'' protein, which contained multiple contiguous minimal murine CTL ep itopes, Mice vaccinated with this plasmid made MHC-restricted CTL resp onses to each of the epitopes, and protective CTL were demonstrated in recombinant vaccinia virus, influenza virus, and tumor challenge mode ls, CTL responses generated by polytope DNA plasmid vaccination lasted for 1 yr, could be enhanced by co-delivering a gene for granulocyte-m acrophage CSF, and appeared to be induced in the absence of CD4 T cell -mediated help, The ability to deliver large numbers of CTL epitopes u sing relatively small polytope constructs and DNA vaccination technolo gy should find application in the design of human epitope-based CTL va ccines, in particular in vaccines against EBV, HIV, and certain cancer s.