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*Substance via MeSH
The Journal of Immunology, 1998, 160: 1717-1723.
Copyright © 1998 by The American Association of Immunologists

Delivery of Multiple CD8 Cytotoxic T Cell Epitopes by DNA Vaccination1

Scott A. Thomson2,*, Martina A. Sherritt2,*, Jill Medveczky{dagger}, Suzanne L. Elliott*, Denis J. Moss*, Germain J. P. Fernando{ddagger}, Lorena E. Brown§ and Andreas Suhrbier3,*

* The Coooperative Research Centre for Vaccine Technology, Queensland Institute of Medical Research, Brisbane, Queensland; {dagger} John Curtin School of Medical Research, Australian National University, Canberra, Australian Capital Territory; {ddagger} 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 {alpha}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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