Natural and long-lasting cellular immune responses against influenza in the M2e-immune host.
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.
Department for Molecular Biomedical Research, VIB, Ghent, Belgium.
M
M
Schotsaert
T
T
Ysenbaert
K
K
Neyt
L I
LI
Ibañez
P
P
Bogaert
B
B
Schepens
B N
BN
Lambrecht
W
W
Fiers
X
X
Saelens
D000818:Animals; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology; D003429:Cross Reactions / Q000276:immunology; D004195:Disease Models, Animal; D005260:Female; D054884:Host-Pathogen Interactions / Q000276:immunology; D007111:Immunity, Cellular; D053118:Influenza A Virus, H1N1 Subtype / Q000276:immunology*; D007252:Influenza Vaccines / Q000276:immunology*; D008168:Lung / Q000276:immunology / Q000821:virology; D051379:Mice; D009976:Orthomyxoviridae Infections / Q000517:prevention & control* / Q000821:virology; D014763:Viral Matrix Proteins / Q000276:immunology*
D007252:Influenza Vaccines; D014763:Viral Matrix Proteins