title: Immunogenicity of modified vaccinia virus Ankara expressing the hemagglutinin stalk domain of pandemic (H1N1) 2009 influenza virus.
abstract: BACKGROUND
  Vaccination offers protection against influenza, although current vaccines need to be reformulated each year. The development of a broadly protective influenza vaccine would guarantee the induction of heterosubtypic immunity also against emerging influenza viruses of a novel subtype. Vaccine candidates based on the stalk region of the hemagglutinin (HA) have the potential to induce broad and persistent protection against diverse influenza A viruses.
  
  
  METHODS
  Modified vaccinia virus Ankara (MVA) expressing a headless HA (hlHA) of A/California/4/09 (CA/09) virus was used as a vaccine to immunize C57BL/6 mice. Specific antibody and cell-mediated immune responses were determined, and challenge experiments were performed by infecting vaccinated mice with CA/09 virus.
  
  
  RESULTS
  Immunization of mice with CA/09-derived hlHA, vectored by MVA, was able to elicit influenza-specific broad cross-reactive antibodies and cell-mediated immune responses, but failed to induce neutralizing antibodies and did not protect mice against virus challenge.
  
  
  CONCLUSIONS
  Although highly immunogenic, our vaccine was unable to induce a protective immunity against influenza. A misfolded and unstable conformation of the hlHA molecule may have affected its capacity of inducing neutralizing antiviral, conformational antibodies. Design of stable hlHA-based immunogens and their delivery by recombinant MVA-based vectors has the potential of improving this promising approach for 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: 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: Francesco
authors.initials: F
authors.lastname: Gubinelli
authors.affiliation: b Molecular Immunology Unit , San Raffaele Research Institute , Milan , Italy.
authors.forename: Maddalena
authors.initials: M
authors.lastname: Panigada
authors.affiliation: a Department of Infectious Diseases , Istituto Superiore di Sanità , Rome , Italy.
authors.forename: Marzia
authors.initials: M
authors.lastname: Facchini
authors.affiliation: a Department of Infectious Diseases , Istituto Superiore di Sanità , Rome , Italy.
authors.forename: Concetta
authors.initials: C
authors.lastname: Fabiani
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: d Polo d'Innovazione della Genomica, Genetica e Biologia , University of Perugia , Perugia , Italy.
authors.forename: Michela
authors.initials: M
authors.lastname: Basileo
authors.affiliation: d Polo d'Innovazione della Genomica, Genetica e Biologia , University of Perugia , Perugia , Italy.
authors.forename: Antonio
authors.initials: A
authors.lastname: Cassone
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; D056738:Cross Protection / Q000276:immunology; D005822:Genetic Vectors; D019267:Hemagglutinin Glycoproteins, Influenza Virus / Q000378:metabolism*; D007111:Immunity, Cellular; D053118:Influenza A Virus, H1N1 Subtype / Q000276:immunology*; D007252:Influenza Vaccines / Q000276:immunology*; D008810:Mice, Inbred C57BL; 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; D019267:Hemagglutinin Glycoproteins, Influenza Virus; D007252:Influenza Vaccines; D014614:Vaccines, Synthetic; D014764:Viral Proteins
keywords: Influenza virus; MVA vector; antibodies; vaccine