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Pandemic H1N1 influenza vaccine induces a recall response in humans that favors broadly cross-reactive memory B cells

Open access
Li, Gui-Mei, Chiu, Christopher, Wrammert, Jens, McCausland, Megan, Andrews, Sarah F., Zheng, Nai-Ying, Lee, Jane-Hwei, Huang, Min, Qu, Xinyan, Edupuganti, Srilatha, Mulligan, Mark, Das, Suman R., Yewdell, Jonathan W., Mehta, Aneesh K., Wilson, Patrick C., Ahmed, Rafi·2012·Proceedings of the National Academy of Sciences

Abstract

We have previously shown that broadly neutralizing antibodies reactive to the conserved stem region of the influenza virus hemagglutinin (HA) were generated in people infected with the 2009 pandemic H1N1 strain. Such antibodies are rarely seen in humans following infection or vaccination with seasonal influenza virus strains. However, the important question remained whether the inactivated 2009 pandemic H1N1 vaccine, like the infection, could also induce these broadly neutralizing antibodies. To address this question, we analyzed B-cell responses in 24 healthy adults immunized with the pandemic vaccine in 2009. In all cases, we found a rapid, predominantly IgG-producing vaccine-specific plasmablast response. Strikingly, the majority (25 of 28) of HA-specific monoclonal antibodies generated from the vaccine-specific plasmablasts neutralized more than one influenza strain and exhibited high levels of somatic hypermutation, suggesting they were derived from recall of B-cell memory. Indeed, memory B cells that recognized the 2009 pandemic H1N1 HA were detectable before vaccination not only in this cohort but also in samples obtained before the emergence of the pandemic strain. Three antibodies demonstrated extremely broad cross-reactivity and were found to bind the HA stem. Furthermore, one stem-reactive antibody recognized not only H1 and H5, but also H3 influenza viruses. This exceptional cross-reactivity indicates that antibodies capable of neutralizing most influenza subtypes might indeed be elicited by vaccination. The challenge now is to improve upon this result and design influenza vaccines that can elicit these broadly cross-reactive antibodies at sufficiently high levels to provide heterosubtypic protection.

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Metadata

Authors
Li, G.-M., Chiu, C., Wrammert, J., McCausland, M., Andrews, S. F., Zheng, N.-Y., Lee, J.-H., Huang, M., Qu, X., Edupuganti, S., Mulligan, M., Das, S. R., Yewdell, J. W., Mehta, A. K., Wilson, P. C., & Ahmed, R.
Venue
Proceedings of the National Academy of Sciences
Published
2012-05-21
Volume
109
Issue
23
Pages
9047-9052
ISSN
  • 0027-8424 (ISSN-L)
  • 1091-6490
OpenAlex
W2076213364
Cited by
393
References
20
FWCI
26.07
Type
journal article
Language
en
Open access
green

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CoChat. (2026). Citation check: Pandemic H1N1 influenza vaccine induces a recall response in humans that favors broadly cross-reactive memory B cells. https://app.cochat.ai/papers/10.1073/pnas.1118979109
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Li, G.-M., Chiu, C., Wrammert, J., McCausland, M., Andrews, S. F., Zheng, N.-Y., Lee, J.-H., Huang, M., Qu, X., Edupuganti, S., Mulligan, M., Das, S. R., Yewdell, J. W., Mehta, A. K., Wilson, P. C., & Ahmed, R. (2012). Pandemic H1N1 influenza vaccine induces a recall response in humans that favors broadly cross-reactive memory B cells. Proceedings of the National Academy of Sciences. https://doi.org/10.1073/pnas.1118979109

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