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Long-lasting cross-protection against influenza A by neuraminidase and M2e-based immunization strategies

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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.
Keywords
A/H5N1 VIRUS, MICE, A/H3N2 VIRUS, VIRAL NEURAMINIDASE, PANDEMIC H1N1, HETEROSUBTYPIC IMMUNITY, LETHAL INFECTION, VIRUS-INFECTION, T-CELL IMMUNITY, LYMPHOID-TISSUE IBALT

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Chicago
Schotsaert, Michael, Tine Ysenbaert, Anouk Smet, Bert Schepens, Dieter Vanderschaeghe, Svetlana Stegalkina, Thorsten U Vogel, Nico Callewaert, Walter Fiers, and Xavier Saelens. 2016. “Long-lasting Cross-protection Against Influenza A by Neuraminidase and M2e-based Immunization Strategies.” Scientific Reports 6.
APA
Schotsaert, M., Ysenbaert, T., Smet, A., Schepens, B., Vanderschaeghe, D., Stegalkina, S., Vogel, T. U., et al. (2016). Long-lasting cross-protection against influenza A by neuraminidase and M2e-based immunization strategies. SCIENTIFIC REPORTS, 6.
Vancouver
1.
Schotsaert M, Ysenbaert T, Smet A, Schepens B, Vanderschaeghe D, Stegalkina S, et al. Long-lasting cross-protection against influenza A by neuraminidase and M2e-based immunization strategies. SCIENTIFIC REPORTS. 2016;6.
MLA
Schotsaert, Michael, Tine Ysenbaert, Anouk Smet, et al. “Long-lasting Cross-protection Against Influenza A by Neuraminidase and M2e-based Immunization Strategies.” SCIENTIFIC REPORTS 6 (2016): n. pag. Print.
@article{7250786,
  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.},
  articleno    = {24402},
  author       = {Schotsaert, Michael and Ysenbaert, Tine and Smet, Anouk and Schepens, Bert and Vanderschaeghe, Dieter and Stegalkina, Svetlana and Vogel, Thorsten U and Callewaert, Nico and Fiers, Walter and Saelens, Xavier},
  issn         = {2045-2322},
  journal      = {SCIENTIFIC REPORTS},
  language     = {eng},
  pages        = {22},
  title        = {Long-lasting cross-protection against influenza A by neuraminidase and M2e-based immunization strategies},
  url          = {http://dx.doi.org/10.1038/srep24402},
  volume       = {6},
  year         = {2016},
}

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