Sequencing Antibody Repertoires Provides Evidence for Original Antigenic Sin Shaping the Antibody Response to Influenza Vaccination

[Emily]

http://www.sciencedirect.com/science/article/pii/S1521661614000035

Clinical Immunology
Available online 9 January 2014
Sequencing Antibody Repertoires Provides Evidence for Original Antigenic Sin Shaping the Antibody Response to Influenza Vaccination

Yann-Chong Tana, b, c,
Lisa K. Scalfonea, b,
Sarah Kongpachitha, b, c,
Chia-Hsin Jua, b,
Xiaoyong Caia, b,
Tamsin M. Lindstromb,
Jeremy Sokolovea, b,
William H. Robinsona, b, c

Highlights

<dl class="listitem" id="list_l0005"><dt class="label">?</dt><dd>Deep-sequencing of plasmablast antibody repertoires to influenza vaccination.
</dd><dt class="label">?</dt><dd>Single-cell barcoding enables recovery of natively paired heavy- and light-chains.
</dd><dt class="label">?</dt><dd>Identification of clonal families of antibodies with shared rearrangements.
</dd><dt class="label">?</dt><dd>Antibodies from clonal populations are enriched for binding and neutralization.
</dd><dt class="label">?</dt><dd>Some antibodies induced by influenza vaccination exhibit original antigenic sin.
</dd></dl>
<hr id="abs_authorab00051" class="artHeader">Abstract

We used a DNA barcoding method to enable high-throughput sequencing of the cognate heavy- and light-chain pairs of expressed antibodies. We used this approach to elucidate the plasmablast antibody response to influenza vaccination. We show that > 75% of the rationally selected plasmablast antibodies bind and neutralize influenza, and that antibodies from clonal families, defined by sharing both heavy chain VJ and light chain VJ sequence usage, do so most effectively. Vaccine-induced heavy chain VJ regions contained on average > 20 nucleotide mutations as compared to their predicted germline gene sequences, and some vaccine-induced antibodies exhibited higher binding affinities for hemagglutinins derived from prior years? seasonal influenza as compared to their affinities for the immunization strains. Our results show that influenza vaccination induces the recall of memory B cells that express antibodies that previously underwent affinity maturation against prior years? seasonal influenza, suggesting that ?original antigenic sin? shapes the antibody response to influenza vaccination.

Keywords

• Antibody;
• Influenza;
• B cell

<dl class="footnote" id="item1" data-t="n"><dt class="label">☆</dt><dd>This is an open-access article distributed under the terms of the Creative Commons Attribution-NonCommercial-No Derivative Works License, which permits non-commercial use, distribution, and reproduction in any medium, provided the original author and source are credited.
</dd></dl><dl class="correspondence" id="cr0005"><dt class="label topPadd"></dt><dd>Corresponding author at: VA Palo Alto Health Care System, 3801 Miranda Ave, Palo Alto, CA 94304 USA.</dd></dl>
Copyright ? 2013 The Authors. Published by Elsevier Inc. All rights reserved.