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Author Notes:

CORRESPONDENCE Scott E. Hensley: shensley@wistar.org

Author contributions: S.E. Hensley, P.C. Wilson, R. Ahmed, T.M. Ross, S. Esposito, N. Principi, and J. Wrammert designed and supervised experiments. Y. Li, J.L. Myers, C.B. Sullivan., J. Madara, S.L. Linderman, D.M. Carter, and J. Wrammert performed experiments.

D.L. Bostick and J.B. Plotkin completed computational modeling.

Q. Liu and Y. Li completed statistical analyses.

S.E. Hensley and Y. Li wrote the paper with input from all authors.

R. Ahmed., J. Wrammert, and P.C. Wilson have a licensing agreement with MedImmune on the influenza virus-specific human monoclonal antibodies.

There are no further conflicting financial interests.

Subjects:

Research Funding:

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.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.

D.L. Bostick is also supported by the NIH (NIH T32A1055400).

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.

Computational support from the San Diego Supercomputing Center is gratefully acknowledged.

We acknowledge support from Jeffrey Faust and the Wistar Institute Flow Cytometry Facility.

This work used the Extreme Science and Engineering Discovery Environment (XSEDE), which is supported by National Science Foundation grant number OCI-1053575.

Keywords:

  • Science & Technology
  • Life Sciences & Biomedicine
  • Immunology
  • Medicine, Research & Experimental
  • Research & Experimental Medicine
  • SWINE-ORIGIN 2009
  • VIRUS HEMAGGLUTININ
  • RECOGNIZES
  • VACCINE
  • HUMANS

Immune history shapes specificity of pandemic H1N1 influenza antibody responses

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Journal Title:

Journal of Experimental Medicine

Volume:

Volume 210, Number 8

Publisher:

, Pages 1493-1500

Type of Work:

Article | Final Publisher PDF

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.

Copyright information:

© 2013 Li et al.

This is an Open Access work distributed under the terms of the Creative Commons Attribution-NonCommercial-ShareAlike 3.0 Unported License (http://creativecommons.org/licenses/by-nc-sa/3.0/).

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