title: Protective immunity against influenza in HLA-A2 transgenic mice by modified vaccinia virus Ankara vectored vaccines containing internal influenza proteins.
abstract: BACKGROUND
  The emergence of novel strains of influenza A viruses with hemagglutinins (HAs) that are antigenically distinct from those circulating in humans, and thus have pandemic potential, pose concerns and call for the development of more broadly protective influenza vaccines. In the present study, modified vaccinia virus Ankara (MVA) encoding internal influenza antigens were evaluated for their immunogenicity and ability to protect HLA-A2.1 transgenic (AAD) mice from infection with influenza viruses.
  
  
  METHODS
  MVAs expressing NP (MVA-NP), M1 (MVA-M1) or polymerase PB1 (MVA-PB1) of A/California/4/09 (CA/09) virus were generated and used to immunize AAD mice. Antibodies and CD8+T cell responses were assessed by ELISA and ELISPOT, respectively, and challenge experiments were performed by infecting vaccinated mice with CA/09 virus.
  
  
  RESULTS
  CD8+T cells specific to immunodominant and subdominant epitopes on the internal influenza proteins were elicited by MVA-based vectors in AAD mice, whereas influenza-specific antibodies were detected only in MVA-NP-immunized mice. Both M1- and NP-based MVA vaccines, regardless of whether they were applied individually or in combination, conferred protection against lethal influenza virus challenge.
  
  
  CONCLUSIONS
  Our data further emphasize the promising potential of MVA vector expressing internal antigens toward the development of a universal influenza vaccine.
authors.affiliation: a Department of Infectious Diseases , Istituto Superiore di Sanità , Rome , Italy.
authors.forename: Giuseppina
authors.initials: G
authors.lastname: Di Mario
authors.affiliation: a Department of Infectious Diseases , Istituto Superiore di Sanità , Rome , Italy.
authors.forename: Ester
authors.initials: E
authors.lastname: Sciaraffia
authors.affiliation: a Department of Infectious Diseases , Istituto Superiore di Sanità , Rome , Italy.
authors.forename: Marzia
authors.initials: M
authors.lastname: Facchini
authors.affiliation: b Molecular Immunology Unit , San Raffaele Research Institute , Milan , Italy.
authors.forename: Francesco
authors.initials: F
authors.lastname: Gubinelli
authors.affiliation: b Molecular Immunology Unit , San Raffaele Research Institute , Milan , Italy.
authors.forename: Elisa
authors.initials: E
authors.lastname: Soprana
authors.affiliation: b Molecular Immunology Unit , San Raffaele Research Institute , Milan , Italy.
authors.forename: Maddalena
authors.initials: M
authors.lastname: Panigada
authors.affiliation: b Molecular Immunology Unit , San Raffaele Research Institute , Milan , Italy.
authors.forename: Valentina
authors.initials: V
authors.lastname: Bernasconi
authors.affiliation: c Department of Biology and Biotechnology "Charles Darwin" , Sapienza University of Rome , Rome , Italy.
authors.forename: Bruno
authors.initials: B
authors.lastname: Garulli
authors.affiliation: b Molecular Immunology Unit , San Raffaele Research Institute , Milan , Italy.
authors.forename: Antonio
authors.initials: A
authors.lastname: Siccardi
authors.affiliation: a Department of Infectious Diseases , Istituto Superiore di Sanità , Rome , Italy.
authors.forename: Isabella
authors.initials: I
authors.lastname: Donatelli
authors.affiliation: a Department of Infectious Diseases , Istituto Superiore di Sanità , Rome , Italy.
authors.forename: Maria R
authors.initials: MR
authors.lastname: Castrucci
mesh_terms: D000818:Animals; D000914:Antibodies, Viral / Q000096:biosynthesis; D000956:Antigens, Viral / Q000276:immunology; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology; D005822:Genetic Vectors; D015789:HLA-A2 Antigen / Q000235:genetics; D006801:Humans; D007111:Immunity, Cellular; D007252:Influenza Vaccines / Q000276:immunology*; D008822:Mice, Transgenic; D009975:Orthomyxoviridae / Q000276:immunology; D009976:Orthomyxoviridae Infections / Q000276:immunology / Q000517:prevention & control*; D014614:Vaccines, Synthetic / Q000276:immunology; D014616:Vaccinia virus / Q000276:immunology*; D014764:Viral Proteins / Q000276:immunology
chemical_list: D000914:Antibodies, Viral; D000956:Antigens, Viral; D015789:HLA-A2 Antigen; D007252:Influenza Vaccines; D014614:Vaccines, Synthetic; D014764:Viral Proteins
keywords: Influenza virus; MVA vector; internal proteins; transgenic mice; vaccine