Abstract
Human papillomavirus type 16 (HPV-16) infection is associated with a majority of cervical cancers and a significant proportion of head and neck cancers. Here, we describe a novel-engineered DNA vaccine that encodes a HPV-16 consensus E6/E7 fusion gene (pConE6E7) with the goal of increasing its antitumor cellular immunity. Compared to an early stage HPV-16 E7 DNA vaccine (pE7), this construct was up to five times more potent in driving E7-specific cellular immune responses. Prophylactic administration of this vaccine resulted in 100% protection against HPV E6 and E7-expressing tumors. Therapeutic studies indicated that vaccination with pConE6E7 prevented or delayed the growth of tumors. Moreover, immunization with pConE6E7 could also partially overcome immune tolerance in E6/E7 transgenic mice. Such DNA immunogens are interesting candidates for further study to investigate mechanisms of tumor immune rejection in vivo.
Publication types
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Research Support, N.I.H., Extramural
MeSH terms
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Amino Acid Sequence
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Animals
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Antigens, Viral / genetics
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Antigens, Viral / immunology*
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Base Sequence
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DNA, Viral / chemistry
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DNA, Viral / genetics
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Female
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Human papillomavirus 16 / genetics
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Human papillomavirus 16 / immunology*
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Mice
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Mice, Inbred C57BL
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Mice, Transgenic
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Molecular Sequence Data
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Neoplasms / pathology
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Neoplasms / prevention & control
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Oncogene Proteins, Viral / genetics
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Oncogene Proteins, Viral / immunology*
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Papillomavirus E7 Proteins
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Papillomavirus Vaccines / genetics
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Papillomavirus Vaccines / immunology*
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Recombinant Fusion Proteins / genetics
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Recombinant Fusion Proteins / immunology
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Repressor Proteins / genetics
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Repressor Proteins / immunology*
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Sequence Analysis, DNA
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Vaccines, DNA / genetics
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Vaccines, DNA / immunology*
Substances
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Antigens, Viral
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DNA, Viral
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E6 protein, Human papillomavirus type 16
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Oncogene Proteins, Viral
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Papillomavirus E7 Proteins
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Papillomavirus Vaccines
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Recombinant Fusion Proteins
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Repressor Proteins
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Vaccines, DNA
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oncogene protein E7, Human papillomavirus type 16