Journal article
The kinase mTOR modulates the antibody response to provide cross-protective immunity to lethal infection with influenza virus
R Keating, T Hertz, M Wehenkel, TL Harris, BA Edwards, JL McClaren, SA Brown, S Surman, ZS Wilson, P Bradley, J Hurwitz, H Chi, PC Doherty, PG Thomas, MA McGargill
Nature Immunology | NATURE PUBLISHING GROUP | Published : 2013
DOI: 10.1038/ni.2741
Abstract
Highly pathogenic avian influenza viruses pose a continuing global threat. Current vaccines will not protect against newly evolved pandemic viruses. The creation of 'universal' vaccines has been unsuccessful because the immunological mechanisms that promote heterosubtypic immunity are incompletely defined. We found here that rapamycin, an immunosuppressive drug that inhibits the kinase mTOR, promoted cross-strain protection against lethal infection with influenza virus of various subtypes when administered during immunization with influenza virus subtype H3N2. Rapamycin reduced the formation of germinal centers and inhibited class switching in B cells, which yielded a unique repertoire of an..
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Awarded by National Institutes of Health
Funding Acknowledgements
We thank H. Zeng (St. Jude Children's Research Hospital) for mice with inducible deletion of Rptor in B cells; B. Creasy and T. Oguin for technical support; P. Vogel and the Veterinary Pathology Core at St. Jude for histology; and S. Patrick and the staff of the Shared Animal Resource Center at St. Jude Children's Research Hospital for animal husbandry. Supported by the National Institute of Allergy and Infectious Diseases of the US National Institutes of Health, Department of Health and Human Services (HHSN266200700005C) and American Lebanese Syrian Associated Charities.