Diverse Heterologous Primary Infections Radically Alter Immunodominance Hierarchies and Clinical Outcomes Following H7N9 Influenza Challenge in Mice
Susu Duan, Victoria A Meliopoulos, Jennifer L McClaren, Xi-Zhi J Guo, Catherine J Sanders, Heather S Smallwood, Richard J Webby, Stacey L Schultz-Cherry, Peter C Doherty, Paul G Thomas
PLoS Pathogens | PUBLIC LIBRARY SCIENCE | Published : 2015
The recent emergence of a novel H7N9 influenza A virus (IAV) causing severe human infections in China raises concerns about a possible pandemic. The lack of pre-existing neutralizing antibodies in the broader population highlights the potential protective role of IAV-specific CD8(+) cytotoxic T lymphocyte (CTL) memory specific for epitopes conserved between H7N9 and previously encountered IAVs. In the present study, the heterosubtypic immunity generated by prior H9N2 or H1N1 infections significantly, but variably, reduced morbidity and mortality, pulmonary virus load and time to clearance in mice challenged with the H7N9 virus. In all cases, the recall of established CTL memory was character..View full abstract
Awarded by National Institute of Allergy and Infectious Disease, US National Institutes of Health
Awarded by NATIONAL INSTITUTE OF ALLERGY AND INFECTIOUS DISEASES
This work was supported by R01AI107625 and HHSN266200700005C awarded to PGT, from the National Institute of Allergy and Infectious Disease, US National Institutes of Health, and ALSAC at SJCRH. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.