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15 Jul 2013

Immune history shapes specificity of pandemic H1N1 influenza antibody responses (J Exp Med., abstract, edited)

[Source: Journal of Experimental Medicine, full page: (LINK). Abstract, edited.]

Published July 15, 2013 / The Rockefeller University Press, doi: 10.1084/jem.20130212 © 2013 Li et al.

Brief Definitive Report

Immune history shapes specificity of pandemic H1N1 influenza antibody responses

Yang Li 1,2, Jaclyn L. Myers 1, David L. Bostick 4, Colleen B. Sullivan 1, Jonathan Madara 1,2, Susanne L. Linderman 1,3, Qin Liu 1, Donald M. Carter 5,6, Jens Wrammert 7,8, Susanna Esposito 9, Nicola Principi 9, Joshua B. Plotkin 4, Ted M. Ross 5,6, Rafi Ahmed 7,8, Patrick C. Wilson 10, and Scott E. Hensley 1,2,3

Author Affiliations: 1Wistar Institute, Philadelphia, PA 19104 2Department of Microbiology and 3Institute for Immunology, University of Pennsylvania Perelman School of Medicine, Philadelphia, PA 19104 4Department of Biology, University of Pennsylvania, Philadelphia, PA 19104 5Center for Vaccine Research and 6Department of Microbiology and Molecular Genetics, University of Pittsburgh, Pittsburgh, PA 15261 7Emory Vaccine Center and 8Department of Microbiology and Immunology, Emory University School of Medicine, Atlanta, GA 30322 9Pediatric Clinic 1, Department of Pathophysiology and Transplantation, Universita degli Studi di Milano, Fondazione IRCCS Ca’ Granda Ospedale Maggiore Policlinico, 20122 Milan, Italy  10Department of Medicine, University of Chicago, Chicago, IL 60637




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 a critical K133 amino acid in this HA epitope, whereas this amino acid is either mutated or deleted 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.

Submitted: 29 January 2013  - Accepted: 26 June 2013

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