Protection against H5N1 Influenza Virus Induced by Matrix-M Adjuvanted Seasonal Virosomal Vaccine in Mice Requires Both Antibodies and T Cells

• Published in: PloS one 2015-12, Vol.10 (12), p.e0145243-e0145243
• Main Authors: Cox, Freek, Baart, Matthijs, Huizingh, Jeroen, Tolboom, Jeroen, Dekking, Liesbeth, Goudsmit, Jaap, Saeland, Eirikur, Radošević, Katarina
• Format: Article
• Language: English
• Subjects: Animals; Antibodies; Antibodies, Viral - immunology; Avian flu; Avian influenza; B cells; Binding sites; CD4 antigen; CD8 antigen; Cross-protection; Cytotoxicity; Depletion; Disease prevention; Epidemics; Exo-a-sialidase; Female; Hemagglutination; Hemagglutinins; Immune response (cell-mediated); Immune response (humoral); Immune system; Immunity, Cellular; Immunity, Humoral; Immunoglobulins; Immunology; Infections; Infectious diseases; Influenza; Influenza A Virus, H5N1 Subtype - immunology; Influenza vaccines; Influenza Vaccines - immunology; Influenza Vaccines - pharmacokinetics; Lectins; Lymphocytes; Lymphocytes T; Mice; Mice, Inbred BALB C; Orthomyxoviridae Infections - immunology; Orthomyxoviridae Infections - prevention & control; Outbreaks; Pandemics; Pharmaceutical industry; Proteins; R&D; Research & development; T cells; T-Lymphocytes - immunology; Toxicity; Vaccines; Viruses; Zoonoses
• ISSN: 1932-6203; 1932-6203
• DOI: 10.1371/journal.pone.0145243

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. 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. 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. 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.