Abstract
At present few vaccine candidates exists against potentially pandemic influenza virus infections. We provide compelling evidence that a targeted fusion protein based on the CTA1-DD adjuvant and containing tandem repeats of the matrix protein 2 (M2e) ectodomain epitope, CTA1-3M2e-DD, confers strong protective immunity against a potentially lethal challenge infection with influenza virus in mice. The formulation was highly effective for mucosal immunizations and promoted high M2e-specific serum IgG and mucosal IgA antibody titers and an hitherto unknown anti-M2e CD4 T cell immunity. This novel CTA1-3M2e-DD fusion protein combines adjuvant and a conserved influenza A antigen in a promising candidate for a universal anti-influenza vaccine.
Publication types
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Research Support, N.I.H., Extramural
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Research Support, Non-U.S. Gov't
MeSH terms
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Adjuvants, Immunologic / administration & dosage*
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Amino Acid Sequence
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Animals
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Antibodies, Viral / blood
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B-Lymphocytes / immunology
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Cholera Toxin / administration & dosage
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Cholera Toxin / immunology*
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Female
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Immunity, Mucosal*
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Immunization
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Immunoglobulin A / analysis
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Immunoglobulin G / blood
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Influenza A Virus, H1N1 Subtype / genetics
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Influenza A Virus, H1N1 Subtype / pathogenicity
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Influenza A Virus, H3N2 Subtype / genetics
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Influenza A Virus, H3N2 Subtype / pathogenicity
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Influenza Vaccines / administration & dosage
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Influenza Vaccines / genetics
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Influenza Vaccines / immunology*
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Male
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Mice
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Molecular Sequence Data
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Orthomyxoviridae Infections / immunology*
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Orthomyxoviridae Infections / prevention & control
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Reassortant Viruses / genetics
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Reassortant Viruses / pathogenicity
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Recombinant Fusion Proteins / administration & dosage
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Recombinant Fusion Proteins / genetics
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Recombinant Fusion Proteins / immunology*
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Viral Matrix Proteins / administration & dosage
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Viral Matrix Proteins / chemistry
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Viral Matrix Proteins / genetics
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Viral Matrix Proteins / immunology*
Substances
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Adjuvants, Immunologic
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Antibodies, Viral
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CTA1-DD protein, recombinant
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Immunoglobulin A
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Immunoglobulin G
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Influenza Vaccines
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M2 protein, Influenza A virus
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M2e-HBc influenza vaccine
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Recombinant Fusion Proteins
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Viral Matrix Proteins
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Cholera Toxin