title: Long-Lasting Cross-Protection Against Influenza A by Neuraminidase and M2e-based immunization strategies.
abstract: There is mounting evidence that in the absence of neutralizing antibodies cross-reactive T cells provide protection against pandemic influenza viruses. Here, we compared protection and CD8+ T cell responses following challenge with H1N1 2009 pandemic and H3N2 viruses of mice that had been immunized with hemagglutinin (HA), neuraminidase (NA) and the extracellular domain of matrix protein 2 (M2e) fused to a virus-like particle (VLP). Mice were challenged a first time with a sublethal dose of H1N1 2009 pandemic virus and, four weeks later, challenged again with an H3N2 virus. Mice that had been vaccinated with HA, NA, NA + M2e-VLP and HA + NA + M2e-VLP were protected against homologous H1N1 virus challenge. Challenged NA and NA + M2e-VLP vaccinated mice mounted CD8+ T cell responses that correlated with protection against secondary H3N2 challenge. HA-vaccinated mice were fully protected against challenge with homologous H1N1 2009 virus, failed to mount cross-reactive CD8+ T cells and succumbed to the second challenge with heterologous H3N2 virus. In summary, NA- and M2e-based immunity can protect against challenge with (homologous) virus without compromising the induction of robust cross-reactive CD8+ T cell responses upon exposure to virus.
authors.affiliation: Medical Biotechnology Center, VIB, Ghent, 9052, Belgium.|Department of Biomedical Molecular Biology, Ghent University, Ghent, 9052, Belgium.
authors.forename: Michael
authors.initials: M
authors.lastname: Schotsaert
authors.affiliation: Medical Biotechnology Center, VIB, Ghent, 9052, Belgium.|Department of Biomedical Molecular Biology, Ghent University, Ghent, 9052, Belgium.
authors.forename: Tine
authors.initials: T
authors.lastname: Ysenbaert
authors.affiliation: Medical Biotechnology Center, VIB, Ghent, 9052, Belgium.|Department of Biomedical Molecular Biology, Ghent University, Ghent, 9052, Belgium.
authors.forename: Anouk
authors.initials: A
authors.lastname: Smet
authors.affiliation: Medical Biotechnology Center, VIB, Ghent, 9052, Belgium.|Department of Biomedical Molecular Biology, Ghent University, Ghent, 9052, Belgium.
authors.forename: Bert
authors.initials: B
authors.lastname: Schepens
authors.affiliation: Medical Biotechnology Center, VIB, Ghent, 9052, Belgium.|Department of Biochemistry and Microbiology, Ghent University, Ghent, 9052, Belgium.
authors.forename: Dieter
authors.initials: D
authors.lastname: Vanderschaeghe
authors.affiliation: Sanofi Pasteur, Research North America, Cambridge, Massachusetts, USA.
authors.forename: Svetlana
authors.initials: S
authors.lastname: Stegalkina
authors.affiliation: Sanofi Pasteur, Research North America, Cambridge, Massachusetts, USA.
authors.forename: Thorsten U
authors.initials: TU
authors.lastname: Vogel
authors.affiliation: Medical Biotechnology Center, VIB, Ghent, 9052, Belgium.|Department of Biochemistry and Microbiology, Ghent University, Ghent, 9052, Belgium.
authors.forename: Nico
authors.initials: N
authors.lastname: Callewaert
authors.affiliation: Medical Biotechnology Center, VIB, Ghent, 9052, Belgium.|Department of Biomedical Molecular Biology, Ghent University, Ghent, 9052, Belgium.
authors.forename: Walter
authors.initials: W
authors.lastname: Fiers
authors.affiliation: Medical Biotechnology Center, VIB, Ghent, 9052, Belgium.|Department of Biomedical Molecular Biology, Ghent University, Ghent, 9052, Belgium.
authors.forename: Xavier
authors.initials: X
authors.lastname: Saelens
mesh_terms: D000818:Animals; D057134:Antibodies, Neutralizing / Q000276:immunology; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology; D003429:Cross Reactions; D005260:Female; D006801:Humans; D009980:Influenza A virus / Q000276:immunology* / Q000502:physiology; D007252:Influenza Vaccines / Q000276:immunology; D007251:Influenza, Human / Q000517:prevention & control*; D051379:Mice; D008807:Mice, Inbred BALB C; D009439:Neuraminidase / Q000276:immunology*; D014763:Viral Matrix Proteins / Q000276:immunology*; D014779:Virus Replication; D000086082:Viroporin Proteins
chemical_list: D057134:Antibodies, Neutralizing; D007252:Influenza Vaccines; D009439:Neuraminidase; D014763:Viral Matrix Proteins; C488937:M2 protein, Influenza A virus; D000086082:Viroporin Proteins