期刊
MUCOSAL IMMUNOLOGY
卷 6, 期 2, 页码 276-287出版社
NATURE PUBLISHING GROUP
DOI: 10.1038/mi.2012.69
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资金
- Ghent University
- Belgian Federal Sciences Administration (Federale Wetenschapsbeleid, BELSPO)
- Ghent University IOFgrant Stepstone [IOF08/STEP/001]
- FWO [3G037510]
- Ghent University IOF-grant Stepstone [IOF08/STEP/001]
- Ghent University [BOF09/01M00709]
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.
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