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Nat Med. 2016 Dec;22(12):1456-1464. doi: 10.1038/nm.4224. Epub 2016 Nov 7.

Molecular-level analysis of the serum antibody repertoire in young adults before and after seasonal influenza vaccination.

Author information

1
Department of Chemical Engineering, University of Texas at Austin, Austin, Texas, USA.
2
Center for Systems and Synthetic Biology, University of Texas at Austin, Austin, Texas, USA.
3
Department of Microbiology, Icahn School of Medicine at Mount Sinai, New York, New York, USA.
4
Vaccine Research Center, National Institute of Allergy and Infectious Diseases, US National Institutes of Health, Bethesda, Maryland, USA.
5
Department of Bioengineering, Stanford University, Stanford, California, USA.
6
Department of Biomedical Engineering, University of Texas at Austin, Austin, Texas, USA.
7
Electron Microscopy Laboratory, Cancer Research Technology Program, Leidos Biomedical Research, Inc., Frederick National Laboratory for Cancer Research, Frederick, Maryland, USA.
8
Department of Medicine, Section of Rheumatology, Gwen Knapp Center for Lupus and Immunology Research, University of Chicago, Chicago, Illinois, USA.
9
Department of Pediatrics, Stanford University, Stanford, California, USA.
10
Howard Hughes Medical Institute, Stanford University, Stanford, California, USA.
11
Department of Microbiology and Immunology, Stanford University, Stanford, California, USA.
12
Center for Vaccines and Immunology, Department of Infectious Diseases, University of Georgia, Athens, Georgia, USA.
13
Department of Molecular Biosciences, University of Texas at Austin, Austin, Texas, USA.
14
Department of Applied Physics, Stanford University, Stanford, California, USA.

Abstract

Molecular understanding of serological immunity to influenza has been confounded by the complexity of the polyclonal antibody response in humans. Here we used high-resolution proteomics analysis of immunoglobulin (referred to as Ig-seq) coupled with high-throughput sequencing of transcripts encoding B cell receptors (BCR-seq) to quantitatively determine the antibody repertoire at the individual clonotype level in the sera of young adults before and after vaccination with trivalent seasonal influenza vaccine. The serum repertoire comprised between 40 and 147 clonotypes that were specific to each of the three monovalent components of the trivalent influenza vaccine, with boosted pre-existing clonotypes accounting for ∼60% of the response. An unexpectedly high fraction of serum antibodies recognized both the H1 and H3 monovalent vaccines. Recombinant versions of these H1 + H3 cross-reactive antibodies showed broad binding to hemagglutinins (HAs) from previously circulating virus strains; several of these antibodies, which were prevalent in the serum of multiple donors, recognized the same conserved epitope in the HA head domain. Although the HA-head-specific H1 + H3 antibodies did not show neutralization activity in vitro, they protected mice against infection with the H1N1 and H3N2 virus strains when administered before or after challenge. Collectively, our data reveal unanticipated insights regarding the serological response to influenza vaccination and raise questions about the added benefits of using a quadrivalent vaccine instead of a trivalent vaccine.

PMID:
27820605
PMCID:
PMC5301914
DOI:
10.1038/nm.4224
[Indexed for MEDLINE]
Free PMC Article

Conflict of interest statement

The authors declare no competing financial interests.

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