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PMID: 22615367 Published · ppublish English Journal Article Research Support, American Recovery and Reinvestment Act Research Support, N.I.H., Extramural Research Support, N.I.H., Intramural

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 of the United States of America ·Vol. 109 ·No. 23 ·2012-06-05 ·Pages 9047-52

Li GM, Chiu C, Wrammert J, McCausland M, Andrews SF, Zheng NY, Lee JH, Huang M, Qu X, Edupuganti S, Mulligan M, Das SR, Yewdell JW, Mehta AK, Wilson PC, Ahmed R

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.

MeSH Terms
Adult Antibodies, Monoclonal/immunology B-Lymphocytes/immunology Base Sequence Cross Reactions Enzyme-Linked Immunosorbent Assay Enzyme-Linked Immunospot Assay Flow Cytometry Hemagglutinin Glycoproteins, Influenza Virus/genetics,immunology Humans Immunoglobulin G/immunology Immunoglobulin Variable Region/genetics Immunologic Memory/immunology Influenza A Virus, H1N1 Subtype/immunology Influenza Vaccines/administration & dosage,immunology Influenza, Human/immunology Molecular Sequence Data Neutralization Tests Phylogeny Sequence Analysis, DNA
Chemicals
Antibodies, Monoclonal H1N1 virus hemagglutinin Hemagglutinin Glycoproteins, Influenza Virus Immunoglobulin G Immunoglobulin Variable Region Influenza Vaccines
Authors & Affiliations
16 authors, click to expand affiliations / ORCID
Li Gui-Mei
Emory Vaccine Center, Department of Microbiology and Immunology, School of Medicine, Emory University, Atlanta, GA 30322, USA.
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
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Article Info
Journal
Proceedings of the National Academy of Sciences of the United States of America
Abbr.
Proc Natl Acad Sci U S A
ISSN
1091-6490
DOI
10.1073/pnas.1118979109
Published
2012-06-05
Epub
2012-00-21
Pages
9047-52
Language
English
Region
United States
NLM ID
7505876
PMCID
PMC3384143
Subset
IM
Grants
NIAID NIH HHS · HHSN266200700006C · United States
Medical Research Council · G1000758 · United Kingdom
Medical Research Council · MC_G1001212 · United Kingdom
NIAID NIH HHS · 5U19AI062629-05 · United States
NIAID NIH HHS · U19 AI062629 · United States
NCATS NIH HHS · UL1 TR000454 · United States
Intramural NIH HHS · United States
NIAID NIH HHS · U19 AI057266-06S2 · United States
NIAID NIH HHS · U19-AI057266 · United States
NCRR NIH HHS · UL1 RR025008 · United States
Medical Research Council · G0902266 · United Kingdom
NIAID NIH HHS · U19 AI057266 · United States
NIAID NIH HHS · HHSN266200500026C · United States
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External Links
PubMed source DOI: 10.1073/pnas.1118979109 PMC Full Text View journal details
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