Abstract
The potency of naked DNA vaccines is limited by their inability to amplify and spread in vivo. VP22, a HSV-1 protein, has demonstrated the remarkable property of intercellular transport and may thus provide a unique approach for enhancing vaccine potency. Therefore, we created a novel fusion of VP22 with a model Ag, human papillomavirus type 16 E7, in a DNA vaccine that generated enhanced spreading and MHC class I presentation of AG: These properties led to a dramatic increase in the number of E7-specific CD8(+) T cell precursors in vaccinated mice (around 50-fold) and converted a less effective DNA vaccine into one with significant potency against E7-expressing tumors. In comparison, nonspreading VP22(1-267) mutants failed to enhance vaccine potency. Our data indicated that the potency of DNA vaccines may be dramatically improved through intercellular spreading and enhanced MHC class I presentation of Ag.
Publication types
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Research Support, Non-U.S. Gov't
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Research Support, U.S. Gov't, P.H.S.
MeSH terms
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Adjuvants, Immunologic / administration & dosage
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Adjuvants, Immunologic / genetics
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Adjuvants, Immunologic / metabolism*
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Animals
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Antigen Presentation* / genetics
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Biolistics
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Biological Transport / genetics
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Biological Transport / immunology
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CD8-Positive T-Lymphocytes / immunology
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Cell Line
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Epitopes, T-Lymphocyte / immunology
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Extracellular Space / genetics
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Extracellular Space / immunology*
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Genetic Vectors / administration & dosage
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Genetic Vectors / immunology
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Genetic Vectors / metabolism
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Herpesvirus 1, Human / genetics
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Herpesvirus 1, Human / immunology
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Histocompatibility Antigens Class I / genetics
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Histocompatibility Antigens Class I / immunology*
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Histocompatibility Antigens Class I / metabolism*
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Humans
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Injections, Intradermal
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Lung Neoplasms / immunology
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Lung Neoplasms / prevention & control
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Lung Neoplasms / therapy
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Lymphocyte Activation / genetics
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Mice
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Mice, Inbred C57BL
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Oncogene Proteins, Viral / administration & dosage
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Oncogene Proteins, Viral / genetics
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Oncogene Proteins, Viral / immunology
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Papillomaviridae / genetics
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Papillomaviridae / immunology
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Papillomavirus E7 Proteins
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Stem Cells / immunology
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Vaccines, DNA / administration & dosage
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Vaccines, DNA / immunology*
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Vaccines, DNA / metabolism*
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Viral Structural Proteins / administration & dosage
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Viral Structural Proteins / genetics
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Viral Structural Proteins / immunology
Substances
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Adjuvants, Immunologic
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Epitopes, T-Lymphocyte
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Histocompatibility Antigens Class I
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Oncogene Proteins, Viral
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Papillomavirus E7 Proteins
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Vaccines, DNA
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Viral Structural Proteins
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herpes simplex virus type 1 protein VP22
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oncogene protein E7, Human papillomavirus type 16