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Author Notes:

Corresponding author: Patrick C. Wilson, The University of Chicago, BSLC/Jules F. Knapp Building, 924 East 57th street, R414, Chicago, Illinois 60637, USA. Phone: 773-702-9009, fax: 773-702-1576, wilsonp@uchicago.edu.

SFA and PCW wrote the manuscript and provided intellectual oversight, SFA planned and performed experiments, YH, NTP, CHD, KK, WMT, SL, MH, XQ, JL, MSF, IYH, LIP contributed to the results, FK and PP contributed reagents, JW, RA provided patient samples.

We thank Jori Reigle, Marissa Kumabe, and Elizabeth Yan for help recruiting subjects and collecting blood samples and Nai-Ying Zheng for technical help and guidance.

The authors have no competing interests.


Research Funding:

This work was supported in parts by NIH grants 1U19AI08724 (PCW), 5U54AI057158 (PCW, RA), 5U19AI057266 (PCW, RA, JW), 1U19AI090023 (PCW, RA, JW), 1P01AI097092 (PCW, RA, PP), F32 AI93087 (SFA) and by funds provided by the Gwen Knapp Center for Lupus and Immunology Research.

This work was also partly supported by CRIP (Center for Research on Influenza Pathogenesis), an NIAID funded Center of Excellence for Influenza Research and Surveillance (CEIRS, contract # HHSN266200700010C) (PCW, PP and FK).

Florian Krammer was supported by an Erwin Schrödinger fellowship (J3232) from the Austrian Science Fund (FWF).

Kaval Kaur was supported by a National Science Scholarship (PhD) from the Agency of Science, Technology and Research (A*STAR), Singapore.


  • Science & Technology
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Immune history profoundly affects broadly protective B cell responses to influenza

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Journal Title:

Science Translational Medicine


Volume 7, Number 316


, Pages 316ra192-316ra192

Type of Work:

Article | Post-print: After Peer Review


Generating a broadly protective influenza vaccine is critical to global health. Understanding how immune memory influences influenza immunity is central to this goal. We undertook an in-depth study of the B cell response to the pandemic 2009 H1N1 vaccine over consecutive years. Analysis of monoclonal antibodies generated from vaccineinduced plasmablasts demonstrated that individuals with low preexisting serological titers to the vaccinating strain generated a broadly reactive, hemagglutinin (HA) stalk-biased response. Higher preexisting serum antibody levels correlated with a strain-specific HA head-dominated response. We demonstrate that this HA head immunodominance encompasses poor accessibility of the HA stalk epitopes. Further, we show polyreactivity of HA stalk-reactive antibodies that could cause counterselection of these cells. Thus, preexisting memory B cells against HA head epitopes predominate, inhibiting a broadly protective response against the HA stalk upon revaccination with similar strains. Consideration of influenza exposure history is critical for new vaccine strategies designed to elicit broadly neutralizing antibodies.

Copyright information:

© 2015, American Association for the Advancement of Science

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