title: MVA vectors expressing conserved influenza proteins protect mice against lethal challenge with H5N1, H9N2 and H7N1 viruses.
abstract: BACKGROUND
  The availability of a universal influenza vaccine able to induce broad cross-reactive immune responses against diverse influenza viruses would provide an alternative to currently available strain-specific vaccines. We evaluated the ability of vectors based on modified vaccinia virus Ankara (MVA) expressing conserved influenza proteins to protect mice against lethal challenge with multiple influenza subtypes.
  
  
  METHODS
  Mice were immunized with MVA vectors expressing H5N1-derived nucleoprotein (NP), the stem region of hemagglutinin (HA), matrix proteins 1 and 2 (M1 and M2), the viral polymerase basic protein 1 (PB1), or the HA stem fused to a quadrivalent matrix protein 2 extracellular domain (M2e). Immunized mice were challenged with lethal doses of H5N1, H7N1 or H9N2 virus and monitored for disease symptoms and weight loss. To investigate the influence of previous exposure to influenza virus on protective immune responses induced by conserved influenza proteins, mice were infected with pandemic H1N1 virus (H1N1pdm09) prior to immunization and subsequently challenged with H5N1 virus. Antibody and T cell responses were assessed by ELISA and flow cytometry, respectively.
  
  
  RESULTS
  MVA vectors expressing NP alone, or co-expressed with other conserved influenza proteins, protected mice against lethal challenge with H5N1, H7N1 or H9N2 virus. Pre-exposure to H1N1pdm09 increased protective efficacy against lethal H5N1 challenge. None of the other conserved influenza proteins provided significant levels of protection against lethal challenge. NP-expressing vectors induced high numbers of influenza-specific CD4(+) and CD8(+) T cells and high titer influenza-specific antibody responses. Higher influenza-specific CD4(+) T cell responses and NP-specific CD8(+) T cell responses were associated with increased protective efficacy.
  
  
  CONCLUSIONS
  MVA vectors expressing influenza NP protect mice against lethal challenge with H5N1, H7N1 and H9N2 viruses by a mechanism involving influenza-specific CD4(+) and CD8(+) T cell responses.
authors: Vaccine R&D, Baxter Bioscience, Orth/Donau, Austria.
authors: Annett
authors: A
authors: Hessel
authors: Pharmacology, Baxter Bioscience, Orth/Donau, Austria.
authors: Helga
authors: H
authors: Savidis-Dacho
authors: Pharmacology, Baxter Bioscience, Orth/Donau, Austria.
authors: Sogue
authors: S
authors: Coulibaly
authors: Vaccine R&D, Baxter Bioscience, Orth/Donau, Austria.
authors: Daniel
authors: D
authors: Portsmouth
authors: Global Pathogen Safety, Baxter Bioscience, Vienna, Austria.
authors: Thomas R
authors: TR
authors: Kreil
authors: Vaccine R&D, Baxter Bioscience, Orth/Donau, Austria.
authors: Brian A
authors: BA
authors: Crowe
authors: Vaccine R&D, Baxter Bioscience, Orth/Donau, Austria.
authors: Michael G
authors: MG
authors: Schwendinger
authors: Vaccine R&D, Baxter Bioscience, Orth/Donau, Austria.
authors: Andreas
authors: A
authors: Pilz
authors: Vaccine R&D, Baxter Bioscience, Orth/Donau, Austria.
authors: P Noel
authors: PN
authors: Barrett
authors: Biologicals R&D, Baxter Bioscience, Orth/Donau, Austria.
authors: Falko G
authors: FG
authors: Falkner
authors: Vaccine R&D, Baxter Bioscience, Orth/Donau, Austria.
authors: Birgit
authors: B
authors: Schäfer
mesh_terms: D000818:Animals; D004797:Enzyme-Linked Immunosorbent Assay; D005260:Female; D053124:Influenza A Virus, H5N1 Subtype / Q000276:immunology*; D057916:Influenza A Virus, H7N1 Subtype / Q000276:immunology*; D053127:Influenza A Virus, H9N2 Subtype / Q000276:immunology*; D007252:Influenza Vaccines / Q000276:immunology*; D051379:Mice; D008807:Mice, Inbred BALB C; D009976:Orthomyxoviridae Infections / Q000517:prevention & control* / Q000821:virology; D013601:T-Lymphocytes / Q000276:immunology; D014616:Vaccinia virus / Q000276:immunology*
chemical_list: D007252:Influenza Vaccines