Abstract
Plasmid DNA vaccines encoding full-length antigen often induce both potent antibody and cytotoxic T lymphocyte (CTL) responses. Here, we examine strategies to exclusively elicit epitope-specific CTL responses using DNA constructs expressing a minimal class I MHC-restricted epitope of the nucleoprotein (NP) of influenza virus. The effects of the addition of an ER leader sequence or cytokine combination on minigene-induced CTL responses in vivo were assessed following both delivery by needle injection into skeletal muscle and by gene gun bombardment into skin epidermis. Our data indicate that the leader sequence enhanced the magnitude of the CTL responses, whereas co-injection of the cytokine genes IL-12 and GM-CSF had a minimal effect. An antibody response against NP was not observed in any of the mice receiving the minigene constructs.
Publication types
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Comparative Study
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Research Support, Non-U.S. Gov't
MeSH terms
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Animals
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Antibodies, Viral / biosynthesis
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Antigen Presentation
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Biolistics
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Cytokines / genetics
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Cytokines / immunology
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Epitopes, T-Lymphocyte / administration & dosage
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Epitopes, T-Lymphocyte / genetics
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Epitopes, T-Lymphocyte / immunology*
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Epitopes, T-Lymphocyte / metabolism
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Female
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Genes, Viral / genetics*
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Histocompatibility Antigens Class I / immunology
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Histocompatibility Antigens Class I / metabolism
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Injections, Intramuscular
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Mice
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Mice, Inbred Strains
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Nucleocapsid Proteins
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Nucleoproteins / administration & dosage
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Nucleoproteins / genetics
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Nucleoproteins / immunology
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Nucleoproteins / metabolism
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Orthomyxoviridae / genetics
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Orthomyxoviridae / immunology
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Orthomyxoviridae Infections / immunology
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Orthomyxoviridae Infections / virology
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Peptide Fragments / administration & dosage
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Peptide Fragments / genetics
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Peptide Fragments / immunology
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Peptide Fragments / metabolism
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Plasmids / genetics
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Protein Sorting Signals / genetics
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RNA-Binding Proteins*
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Recombinant Proteins / biosynthesis
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Recombinant Proteins / immunology
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Recombinant Proteins / metabolism
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T-Lymphocytes, Cytotoxic / immunology*
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T-Lymphocytes, Cytotoxic / metabolism
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Tumor Cells, Cultured
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Vaccines, DNA / administration & dosage
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Vaccines, DNA / genetics
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Vaccines, DNA / immunology*
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Viral Core Proteins / administration & dosage
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Viral Core Proteins / genetics
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Viral Core Proteins / immunology
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Viral Core Proteins / metabolism
Substances
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Antibodies, Viral
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Cytokines
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Epitopes, T-Lymphocyte
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Histocompatibility Antigens Class I
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NP protein, Influenza A virus
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Nucleocapsid Proteins
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Nucleoproteins
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Peptide Fragments
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Protein Sorting Signals
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RNA-Binding Proteins
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Recombinant Proteins
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Vaccines, DNA
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Viral Core Proteins