title: Protection against H5N1 Influenza Virus Induced by Matrix-M Adjuvanted Seasonal Virosomal Vaccine in Mice Requires Both Antibodies and T Cells.
abstract: BACKGROUND
  It remains important to develop the next generation of influenza vaccines that can provide protection against vaccine mismatched strains and to be prepared for potential pandemic outbreaks. To achieve this, the understanding of the immunological parameters that mediate such broad protection is crucial.
  
  
  METHODS
  In the current study we assessed the contribution of humoral and cellular immune responses to heterosubtypic protection against H5N1 induced by a Matrix-M (MM) adjuvanted seasonal influenza vaccine by serum transfer and T-cell depletion studies.
  
  
  RESULTS
  We demonstrate that the heterosubtypic protection against H5N1 induced by MM adjuvanted vaccine is partially mediated by antibodies. The serum contained both H5N1 cross-reactive hemagglutinin (HA)- and neuraminidase (NA)-specific antibodies but with limited virus neutralizing and no hemagglutination inhibiting activity. The cross-reactive antibodies induced antibody-dependent cellular cytotoxicity (ADCC) in vitro, suggesting a role for the Fc part of the antibodies in protection against H5N1. Besides H5N1 specific antibody responses, cross-reactive HA- and NA-specific T-cell responses were induced by the adjuvanted vaccine. T-cell depletion experiments demonstrated that both CD4+ and CD8+ T cells contribute to protection.
  
  
  CONCLUSIONS
  Our study demonstrates that cross-protection against H5N1 induced by MM adjuvanted seasonal virosomal influenza vaccine requires both the humoral and cellular arm of the immune system.
authors.affiliation: Janssen Prevention Center, Center of Excellence of Janssen Research & Development, Pharmaceutical companies of Johnson and Johnson, Leiden, The Netherlands.
authors.forename: Freek
authors.initials: F
authors.lastname: Cox
authors.affiliation: Janssen Prevention Center, Center of Excellence of Janssen Research & Development, Pharmaceutical companies of Johnson and Johnson, Leiden, The Netherlands.
authors.forename: Matthijs
authors.initials: M
authors.lastname: Baart
authors.affiliation: Janssen Prevention Center, Center of Excellence of Janssen Research & Development, Pharmaceutical companies of Johnson and Johnson, Leiden, The Netherlands.
authors.forename: Jeroen
authors.initials: J
authors.lastname: Huizingh
authors.affiliation: Janssen Prevention Center, Center of Excellence of Janssen Research & Development, Pharmaceutical companies of Johnson and Johnson, Leiden, The Netherlands.
authors.forename: Jeroen
authors.initials: J
authors.lastname: Tolboom
authors.affiliation: Janssen Prevention Center, Center of Excellence of Janssen Research & Development, Pharmaceutical companies of Johnson and Johnson, Leiden, The Netherlands.
authors.forename: Liesbeth
authors.initials: L
authors.lastname: Dekking
authors.affiliation: Janssen Prevention Center, Center of Excellence of Janssen Research & Development, Pharmaceutical companies of Johnson and Johnson, Leiden, The Netherlands.
authors.forename: Jaap
authors.initials: J
authors.lastname: Goudsmit
authors.affiliation: Janssen Prevention Center, Center of Excellence of Janssen Research & Development, Pharmaceutical companies of Johnson and Johnson, Leiden, The Netherlands.
authors.forename: Eirikur
authors.initials: E
authors.lastname: Saeland
authors.affiliation: Janssen Prevention Center, Center of Excellence of Janssen Research & Development, Pharmaceutical companies of Johnson and Johnson, Leiden, The Netherlands.
authors.forename: Katarina
authors.initials: K
authors.lastname: Radošević
mesh_terms: D000818:Animals; D000914:Antibodies, Viral / Q000276:immunology*; D005260:Female; D007111:Immunity, Cellular; D056724:Immunity, Humoral; D053124:Influenza A Virus, H5N1 Subtype / Q000276:immunology*; D007252:Influenza Vaccines / Q000276:immunology / Q000493:pharmacokinetics*; D051379:Mice; D008807:Mice, Inbred BALB C; D009976:Orthomyxoviridae Infections / Q000276:immunology / Q000517:prevention & control; D013601:T-Lymphocytes / Q000276:immunology*
chemical_list: D000914:Antibodies, Viral; D007252:Influenza Vaccines