Abstract
Development of CD8 alphabeta 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.
Publication types
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Research Support, Non-U.S. Gov't
MeSH terms
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Amino Acid Sequence
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Animals
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Antibodies, Monoclonal / administration & dosage
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Antibody Formation / genetics
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Cytotoxicity, Immunologic / drug effects
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Epitopes, B-Lymphocyte / administration & dosage
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Epitopes, B-Lymphocyte / immunology
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Epitopes, T-Lymphocyte / administration & dosage*
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Epitopes, T-Lymphocyte / immunology*
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Female
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Granulocyte-Macrophage Colony-Stimulating Factor / administration & dosage
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Granulocyte-Macrophage Colony-Stimulating Factor / genetics
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Granulocyte-Macrophage Colony-Stimulating Factor / immunology
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Hemagglutinin Glycoproteins, Influenza Virus / administration & dosage
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Hemagglutinin Glycoproteins, Influenza Virus / genetics
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Hemagglutinin Glycoproteins, Influenza Virus / immunology
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Humans
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Immunologic Memory
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Influenza A virus / immunology
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Injections, Intramuscular
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Lymphocyte Activation / genetics
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Lymphocyte Depletion
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Mice
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Mice, Inbred BALB C
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Mice, Inbred C57BL
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Molecular Sequence Data
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Neoplasm Transplantation
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Plasmids / chemical synthesis
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Plasmids / immunology
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T-Lymphocytes, Cytotoxic / immunology*
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T-Lymphocytes, Helper-Inducer / immunology
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Thymoma
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Vaccination / methods
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Vaccines, DNA / immunology*
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Vaccines, Synthetic / administration & dosage
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Vaccines, Synthetic / immunology
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Vaccinia virus / genetics
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Vaccinia virus / immunology
Substances
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Antibodies, Monoclonal
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Epitopes, B-Lymphocyte
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Epitopes, T-Lymphocyte
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Hemagglutinin Glycoproteins, Influenza Virus
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Vaccines, DNA
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Vaccines, Synthetic
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Granulocyte-Macrophage Colony-Stimulating Factor