Memory T Cells Generated by Prior Exposure to Influenza Cross React with the Novel H7N9 Influenza Virus and Confer Protective Heterosubtypic Immunity

• Type of Material: Article
• Authors: Sean R. McMaster, Emory University; Jon D. Gabbard, University of Georgia; Dimitrios G. Koutsonanos, Emory University; Richard Compans, Emory University; Ralph A. Tripp, University of Georgia; S. Mark Tompkins, University of Georgia; Jacob Kohlmeier, Emory University
• Language: English
• Date: 2015-02-11
• Publisher: Public Library of Science
• Publication Version: Final Published Version
• Copyright Statement: © 2015 McMaster et al.
• License: Creative Commons Attribution 4.0 International
• Final Published Version (URL): http://dx.doi.org/10.1371/journal.pone.0115725
• Title of Journal or Parent Work: PLoS ONE
• ISSN: 1932-6203
• Volume: 10
• Issue: 2
• Start Page: e0115725
• End Page: e0115725
• Grant/Funding Information: This work was supported in part by the Centers of Excellence in Influenza Research and Surveillance (CEIRS) contract number HHSN266200700006C (S.M.T., R.A.T., R.W.C., and J.E.K.) and funds from Emory University. S.R.M. is supported in part by NIH T32 AI007610-14.; The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.
• Keywords: FERRETS; TRANSMISSION; Multidisciplinary Sciences; CHINA; Science & Technology; A(H7N9) VIRUS; A VIRUSES; INFECTION; Science & Technology - Other Topics; EMERGENCE; VACCINATION
• Research Categories: Health Sciences, General; Health Sciences, Immunology

Abstract

Influenza virus is a source of significant health and economic burden from yearly epidemics and sporadic pandemics. Given the potential for the emerging H7N9 influenza virus to cause severe respiratory infections and the lack of exposure to H7 and N9 influenza viruses in the human population, we aimed to quantify the H7N9 cross-reactive memory T cell reservoir in humans and mice previously exposed to common circulating influenza viruses. We identified significant cross-reactive T cell populations in humans and mice; we also found that cross-reactive memory T cells afforded heterosubtypic protection by reducing morbidity and mortality upon lethal H7N9 challenge. In context with our observation that PR8-primed mice have limited humoral cross-reactivity with H7N9, our data suggest protection from H7N9 challenge is indeed mediated by cross-reactive T cell populations established upon previous priming with another influenza virus. Thus, pre-existing cross-reactive memory T cells may limit disease severity in the event of an H7N9 influenza virus pandemic.