title: Vaccine protection against lethal homologous and heterologous challenge using recombinant AAV vectors expressing codon-optimized genes from pandemic swine origin influenza virus (SOIV).
abstract: The recent H1N1 influenza pandemic and the inevitable delay between identification of the virus and production of the specific vaccine have highlighted the urgent need for new generation influenza vaccines that can preemptively induce broad immunity to different strains of the virus. In this study we have produced AAV-based vectors expressing the A/Mexico/4603/2009 (H1N1) hemagglutinin (HA), nucleocapsid (NP) and the matrix protein M1 and have evaluated their ability to induce specific immune response and protect mice against homologous and heterologous challenge. Each of the vaccine vectors elicited potent cellular and humoral immune responses in mice. Although immunization with AAV-M1 did not improve survival after challenge with the homologous strain, immunization with the AAV-H1 and AAV-NP vectors resulted in survival of all mice, as did inoculation with a combination of all three vectors. Furthermore, trivalent vaccination also conferred partial protection against challenge with the highly heterologous and virulent A/PR/8/34 strain of H1N1 influenza.
authors.affiliation: Robert Koch Institute, Nordufer 20, 13353 Berlin, Germany.
authors.forename: Isaac
authors.initials: I
authors.lastname: Sipo
authors.forename: Mathias
authors.initials: M
authors.lastname: Knauf
authors.forename: Henry
authors.initials: H
authors.lastname: Fechner
authors.forename: Wolfgang
authors.initials: W
authors.lastname: Poller
authors.forename: Oliver
authors.initials: O
authors.lastname: Planz
authors.forename: Reinhard
authors.initials: R
authors.lastname: Kurth
authors.forename: Stephen
authors.initials: S
authors.lastname: Norley
mesh_terms: D000256:Adenoviridae / Q000235:genetics / Q000276:immunology; D000818:Animals; D057134:Antibodies, Neutralizing / Q000097:blood; D000914:Antibodies, Viral / Q000097:blood; D005260:Female; D057809:HEK293 Cells; D019267:Hemagglutinin Glycoproteins, Influenza Virus / Q000235:genetics / Q000276:immunology; D006801:Humans; D007111:Immunity, Cellular; D056724:Immunity, Humoral; D053118:Influenza A Virus, H1N1 Subtype / Q000276:immunology*; D007252:Influenza Vaccines / Q000276:immunology*; D007371:Interferon-gamma / Q000276:immunology; D051379:Mice; D008810:Mice, Inbred C57BL; D009500:Neutralization Tests; D019590:Nucleocapsid Proteins; D009976:Orthomyxoviridae Infections / Q000276:immunology / Q000517:prevention & control*; D016601:RNA-Binding Proteins / Q000235:genetics / Q000276:immunology; D014162:Transfection; D014758:Viral Core Proteins / Q000235:genetics / Q000276:immunology; D014763:Viral Matrix Proteins / Q000235:genetics / Q000276:immunology; D010948:Viral Plaque Assay
chemical_list: D057134:Antibodies, Neutralizing; D000914:Antibodies, Viral; D019267:Hemagglutinin Glycoproteins, Influenza Virus; D007252:Influenza Vaccines; C488936:M1 protein, Influenza A virus; C048842:NP protein, Influenza A virus; D019590:Nucleocapsid Proteins; D016601:RNA-Binding Proteins; D014758:Viral Core Proteins; D014763:Viral Matrix Proteins; D007371:Interferon-gamma