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*
The Coooperative Research Centre for Vaccine Technology, Queensland Institute of Medical Research, Brisbane, Queensland;
John Curtin School of Medical Research, Australian National University, Canberra, Australian Capital Territory;
Centre for Immunology and Cancer Research, University of Queensland Department of Medicine, Princess Alexandra Hospital, Brisbane; and
§
Department of Microbiology and Immunology, University of Melbourne, Victoria, Australia
Development of CD8
ß CTL epitope-based vaccines requires an
effective strategy capable of co-delivering large numbers of CTL
epitopes. Here we describe a DNA plasmid encoding a polyepitope or
"polytope" protein, which contained multiple contiguous minimal
murine CTL epitopes. Mice vaccinated with this plasmid made
MHC-restricted CTL responses to each of the epitopes, and protective
CTL were demonstrated in recombinant vaccinia virus, influenza virus,
and tumor challenge models. CTL responses generated by polytope DNA
plasmid vaccination lasted for 1 yr, could be enhanced by co-delivering
a gene for granulocyte-macrophage CSF, and appeared to be induced in
the absence of CD4 T cell-mediated help. The ability to deliver large
numbers of CTL epitopes using relatively small polytope constructs and
DNA vaccination technology should find application in the design of
human epitope-based CTL vaccines, in particular in vaccines against
EBV, HIV, and certain cancers.
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