Immune history shapes specificity of pandemic H1N1 influenza antibody responses

• Type of Material: Article
• Authors: Yang Li, Wistar Institute; Jaclyn L. Myers, Wistar Institute; David L. Bostick, University of Pennsylvania; Colleen B. Sullivan, Wistar Institute; Jonathan Madara, Wistar Institute; Susanne L. Linderman, Wistar Institute; Qin Liu, Wistar Institute; Donald M. Carter, University of Pittsburgh; Jens Wrammert, Emory University; Susanna Esposito, University of Milan; Nicola Principi, University of Milan; Joshua B. Plotkin, University of Pennsylvania; Ted M. Ross, University of Pittsburgh; Rafi Ahmed, Emory University; Patrick C. Wilson, University of Chicago; Scott E. Hensley, Wistar Institute
• Language: English
• Date: 2013-07-29
• Publisher: Rockefeller University Press
• Publication Version: Final Published Version
• Copyright Statement: © 2013 Li et al.
• License: Creative Commons Attribution-NonCommercial-ShareAlike 3.0 Unported
• Final Published Version (URL): http://dx.doi.org/10.1084/jem.20130212
• Title of Journal or Parent Work: Journal of Experimental Medicine
• ISSN: 0022-1007
• Volume: 210
• Issue: 8
• Start Page: 1493
• End Page: 1500
• Grant/Funding Information: This work used the Extreme Science and Engineering Discovery Environment (XSEDE), which is supported by National Science Foundation grant number OCI-1053575.; We acknowledge support from Jeffrey Faust and the Wistar Institute Flow Cytometry Facility.; D.L. Bostick is also supported by the NIH (NIH T32A1055400).; Computational support from the San Diego Supercomputing Center is gratefully acknowledged.; S.E. Hensley is supported by the NIH (NIAID K22AI091651), the state of PA CURE funds, the Wistar Institute Cancer Center Core grant, and a University of Pennsylvania Institute for Translational Medicine and Therapeutics grant.; J. Madara is supported by the Penn Genome Frontiers Institute. T.M. Ross is supported by the NIH (NIAID GM083602-01).; D.M. Carter is supported by an Oak Ridge Visiting Scientist training program award.; J.B. Plotkin and D.L. Bostick are supported by the Burroughs Wellcome Fund, the David and Lucile Packard Foundation, the James S. McDonnell Foundation, the Alfred P. Sloan Foundation, and a University of Pennsylvania Institute for Translational Medicine and Therapeutics grant.
• Keywords: Immunology; Life Sciences & Biomedicine; Science & Technology; SWINE-ORIGIN 2009; Medicine, Research & Experimental; VIRUS HEMAGGLUTININ; RECOGNIZES; VACCINE; HUMANS; Research & Experimental Medicine
• Research Categories: Health Sciences, Immunology; Health Sciences, Public Health

Abstract

Human antibody responses against the 2009 pandemic H1N1 (pH1N1) virus are predominantly directed against conserved epitopes in the stalk and receptor-binding domain of the hemagglutinin (HA) protein. This is in stark contrast to pH1N1 antibody responses generated in ferrets, which are focused on the variable Sa antigenic site of HA. Here, we show that most humans born between 1983 and 1996 elicited pH1N1 antibody responses that are directed against an epitope near the HA receptor-binding domain. Importantly, most individuals born before 1983 or after 1996 did not elicit pH1N1 antibodies to this HA epitope. The HAs of most seasonal H1N1 (sH1N1) viruses that circulated between 1983 and 1996 possess acritical K133 amino acid in this HA epitope, whereas this amino acid is either mutated ordeleted in most sH1N1 viruses circulating before 1983 or after 1996. We sequentially infected ferrets with a 1991 sH1N1 virus and then a pH1N1 virus. Sera isolated from these animals were directed against the HA epitope involving amino acid K133. These data suggest that the specificity of pH1N1 antibody responses can be shifted to epitopes near the HA receptor-binding domain after sequential infections with sH1N1 and pH1N1 viruses that share homology in this region.