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Natural and long-lasting cellular immune responses against influenza in the M2e-immune host

Michael Schotsaert (UGent) , Tine Ysenbaert (UGent) , Kristien Neyts (UGent) , Lorena Ibanez (UGent) , Pieter Bogaert (UGent) , Bert Schepens (UGent) , Bart Lambrecht (UGent) , Walter Fiers and Xavier Saelens (UGent)
(2013) MUCOSAL IMMUNOLOGY. 6(2). p.276-287
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Abstract
Influenza is a global health concern. Licensed influenza vaccines induce strain-specific virus-neutralizing antibodies but hamper the induction of possibly cross-protective T-cell responses upon subsequent infection. (1) In this study, we compared protection induced by a vaccine based on the conserved extracellular domain of matrix 2 protein (M2e) with that of a conventional whole inactivated virus (WIV) vaccine using single as well as consecutive homo-and heterosubtypic challenges. Both vaccines protected against a primary homologous (with respect to hemagglutinin and neuraminidase in WIV) challenge. Functional T-cell responses were induced after primary challenge of M2e-immune mice but were absent in WIV-vaccinated mice. M2e-immune mice displayed limited inducible bronchus-associated lymphoid tissue, which was absent in WIV-immune animals. Importantly, M2e-but not WIV-immune mice were protected from a primary as well as a secondary, severe heterosubtypic challenge, including challenge with pandemic H1N1 2009 virus. Our findings advocate the use of infection-permissive influenza vaccines, such as those based on M2e, in immunologically naive individuals. The combined immune response induced by M2e-vaccine and by clinically controlled influenza virus replication results in strong and broad protection against pandemic influenza. We conclude that the challenge of the M2e-immune host induces strong and broadly reactive immunity against influenza virus infection.
Keywords
A VACCINE, HETEROSUBTYPIC IMMUNITY, HEALTHY-CHILDREN, CD8(+) T-CELLS, EXTRACELLULAR DOMAIN, PROTECTIVE IMMUNITY, MATRIX PROTEIN-2, LETHAL INFECTION, VIRUS-INFECTION, CUTTING EDGE

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Chicago
Schotsaert, Michael, Tine Ysenbaert, Kristien Neyts, Lorena Ibanez, Pieter Bogaert, Bert Schepens, Bart Lambrecht, Walter Fiers, and Xavier Saelens. 2013. “Natural and Long-lasting Cellular Immune Responses Against Influenza in the M2e-immune Host.” Mucosal Immunology 6 (2): 276–287.
APA
Schotsaert, M., Ysenbaert, T., Neyts, K., Ibanez, L., Bogaert, P., Schepens, B., Lambrecht, B., et al. (2013). Natural and long-lasting cellular immune responses against influenza in the M2e-immune host. MUCOSAL IMMUNOLOGY, 6(2), 276–287.
Vancouver
1.
Schotsaert M, Ysenbaert T, Neyts K, Ibanez L, Bogaert P, Schepens B, et al. Natural and long-lasting cellular immune responses against influenza in the M2e-immune host. MUCOSAL IMMUNOLOGY. 2013;6(2):276–87.
MLA
Schotsaert, Michael, Tine Ysenbaert, Kristien Neyts, et al. “Natural and Long-lasting Cellular Immune Responses Against Influenza in the M2e-immune Host.” MUCOSAL IMMUNOLOGY 6.2 (2013): 276–287. Print.
@article{3214560,
  abstract     = {Influenza is a global health concern. Licensed influenza vaccines induce strain-specific virus-neutralizing antibodies but hamper the induction of possibly cross-protective T-cell responses upon subsequent infection. (1) In this study, we compared protection induced by a vaccine based on the conserved extracellular domain of matrix 2 protein (M2e) with that of a conventional whole inactivated virus (WIV) vaccine using single as well as consecutive homo-and heterosubtypic challenges. Both vaccines protected against a primary homologous (with respect to hemagglutinin and neuraminidase in WIV) challenge. Functional T-cell responses were induced after primary challenge of M2e-immune mice but were absent in WIV-vaccinated mice. M2e-immune mice displayed limited inducible bronchus-associated lymphoid tissue, which was absent in WIV-immune animals. Importantly, M2e-but not WIV-immune mice were protected from a primary as well as a secondary, severe heterosubtypic challenge, including challenge with pandemic H1N1 2009 virus. Our findings advocate the use of infection-permissive influenza vaccines, such as those based on M2e, in immunologically naive individuals. The combined immune response induced by M2e-vaccine and by clinically controlled influenza virus replication results in strong and broad protection against pandemic influenza. We conclude that the challenge of the M2e-immune host induces strong and broadly reactive immunity against influenza virus infection.},
  author       = {Schotsaert, Michael and Ysenbaert, Tine and Neyts, Kristien and Ibanez, Lorena and Bogaert, Pieter and Schepens, Bert and Lambrecht, Bart and Fiers, Walter and Saelens, Xavier},
  issn         = {1933-0219},
  journal      = {MUCOSAL IMMUNOLOGY},
  keywords     = {A VACCINE,HETEROSUBTYPIC IMMUNITY,HEALTHY-CHILDREN,CD8(+) T-CELLS,EXTRACELLULAR DOMAIN,PROTECTIVE IMMUNITY,MATRIX PROTEIN-2,LETHAL INFECTION,VIRUS-INFECTION,CUTTING EDGE},
  language     = {eng},
  number       = {2},
  pages        = {276--287},
  title        = {Natural and long-lasting cellular immune responses against influenza in the M2e-immune host},
  url          = {http://dx.doi.org/10.1038/mi.2012.69},
  volume       = {6},
  year         = {2013},
}

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