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Title: Vaccine-Induced Antibodies that Neutralize Group 1 and Group 2 Influenza A Viruses

Abstract

Antibodies capable of neutralizing divergent influenza A viruses could form the basis of a universal vaccine. Here, from subjects enrolled in an H5N1 DNA/MIV-prime-boost influenza vaccine trial, we sorted hemagglutinin cross-reactive memory B cells and identified three antibody classes, each capable of neutralizing diverse subtypes of group 1 and group 2 influenza A viruses. Co-crystal structures with hemagglutinin revealed that each class utilized characteristic germline genes and convergent sequence motifs to recognize overlapping epitopes in the hemagglutinin stem. All six analyzed subjects had sequences from at least one multidonor class, and—in half the subjects—multidonor-class sequences were recovered from >40% of cross-reactive B cells. By contrast, these multidonor-class sequences were rare in published antibody datasets. Vaccination with a divergent hemagglutinin can thus increase the frequency of B cells encoding broad influenza A-neutralizing antibodies. We propose the sequence signature-quantified prevalence of these B cells as a metric to guide universal influenza A immunization strategies.

Authors:
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Publication Date:
Research Org.:
Argonne National Lab. (ANL), Argonne, IL (United States). Advanced Photon Source (APS)
Sponsoring Org.:
National Institutes of Health (NIH); National Institute of Allergy and Infectious Diseases (NIAID); USDOE Office of Science (SC), Basic Energy Sciences (BES)
Contributing Org.:
NISC Comparative Sequencing Program
OSTI Identifier:
1389087
Alternate Identifier(s):
OSTI ID: 1314264
Grant/Contract Number:  
HHSN261200800001E; W-31-109-Eng-38
Resource Type:
Published Article
Journal Name:
Cell
Additional Journal Information:
Journal Name: Cell Journal Volume: 166 Journal Issue: 3; Journal ID: ISSN 0092-8674
Publisher:
Elsevier
Country of Publication:
United States
Language:
English
Subject:
60 APPLIED LIFE SCIENCES

Citation Formats

Joyce, M. Gordon, Wheatley, Adam K., Thomas, Paul V., Chuang, Gwo-Yu, Soto, Cinque, Bailer, Robert T., Druz, Aliaksandr, Georgiev, Ivelin S., Gillespie, Rebecca A., Kanekiyo, Masaru, Kong, Wing-Pui, Leung, Kwanyee, Narpala, Sandeep N., Prabhakaran, Madhu S., Yang, Eun Sung, Zhang, Baoshan, Zhang, Yi, Asokan, Mangaiarkarasi, Boyington, Jeffrey C., Bylund, Tatsiana, Darko, Sam, Lees, Christopher R., Ransier, Amy, Shen, Chen-Hsiang, Wang, Lingshu, Whittle, James R., Wu, Xueling, Yassine, Hadi M., Santos, Celia, Matsuoka, Yumiko, Tsybovsky, Yaroslav, Baxa, Ulrich, Mullikin, James C., Subbarao, Kanta, Douek, Daniel C., Graham, Barney S., Koup, Richard A., Ledgerwood, Julie E., Roederer, Mario, Shapiro, Lawrence, Kwong, Peter D., Mascola, John R., and McDermott, Adrian B.. Vaccine-Induced Antibodies that Neutralize Group 1 and Group 2 Influenza A Viruses. United States: N. p., 2016. Web. https://doi.org/10.1016/j.cell.2016.06.043.
Joyce, M. Gordon, Wheatley, Adam K., Thomas, Paul V., Chuang, Gwo-Yu, Soto, Cinque, Bailer, Robert T., Druz, Aliaksandr, Georgiev, Ivelin S., Gillespie, Rebecca A., Kanekiyo, Masaru, Kong, Wing-Pui, Leung, Kwanyee, Narpala, Sandeep N., Prabhakaran, Madhu S., Yang, Eun Sung, Zhang, Baoshan, Zhang, Yi, Asokan, Mangaiarkarasi, Boyington, Jeffrey C., Bylund, Tatsiana, Darko, Sam, Lees, Christopher R., Ransier, Amy, Shen, Chen-Hsiang, Wang, Lingshu, Whittle, James R., Wu, Xueling, Yassine, Hadi M., Santos, Celia, Matsuoka, Yumiko, Tsybovsky, Yaroslav, Baxa, Ulrich, Mullikin, James C., Subbarao, Kanta, Douek, Daniel C., Graham, Barney S., Koup, Richard A., Ledgerwood, Julie E., Roederer, Mario, Shapiro, Lawrence, Kwong, Peter D., Mascola, John R., & McDermott, Adrian B.. Vaccine-Induced Antibodies that Neutralize Group 1 and Group 2 Influenza A Viruses. United States. https://doi.org/10.1016/j.cell.2016.06.043
Joyce, M. Gordon, Wheatley, Adam K., Thomas, Paul V., Chuang, Gwo-Yu, Soto, Cinque, Bailer, Robert T., Druz, Aliaksandr, Georgiev, Ivelin S., Gillespie, Rebecca A., Kanekiyo, Masaru, Kong, Wing-Pui, Leung, Kwanyee, Narpala, Sandeep N., Prabhakaran, Madhu S., Yang, Eun Sung, Zhang, Baoshan, Zhang, Yi, Asokan, Mangaiarkarasi, Boyington, Jeffrey C., Bylund, Tatsiana, Darko, Sam, Lees, Christopher R., Ransier, Amy, Shen, Chen-Hsiang, Wang, Lingshu, Whittle, James R., Wu, Xueling, Yassine, Hadi M., Santos, Celia, Matsuoka, Yumiko, Tsybovsky, Yaroslav, Baxa, Ulrich, Mullikin, James C., Subbarao, Kanta, Douek, Daniel C., Graham, Barney S., Koup, Richard A., Ledgerwood, Julie E., Roederer, Mario, Shapiro, Lawrence, Kwong, Peter D., Mascola, John R., and McDermott, Adrian B.. Thu . "Vaccine-Induced Antibodies that Neutralize Group 1 and Group 2 Influenza A Viruses". United States. https://doi.org/10.1016/j.cell.2016.06.043.
@article{osti_1389087,
title = {Vaccine-Induced Antibodies that Neutralize Group 1 and Group 2 Influenza A Viruses},
author = {Joyce, M. Gordon and Wheatley, Adam K. and Thomas, Paul V. and Chuang, Gwo-Yu and Soto, Cinque and Bailer, Robert T. and Druz, Aliaksandr and Georgiev, Ivelin S. and Gillespie, Rebecca A. and Kanekiyo, Masaru and Kong, Wing-Pui and Leung, Kwanyee and Narpala, Sandeep N. and Prabhakaran, Madhu S. and Yang, Eun Sung and Zhang, Baoshan and Zhang, Yi and Asokan, Mangaiarkarasi and Boyington, Jeffrey C. and Bylund, Tatsiana and Darko, Sam and Lees, Christopher R. and Ransier, Amy and Shen, Chen-Hsiang and Wang, Lingshu and Whittle, James R. and Wu, Xueling and Yassine, Hadi M. and Santos, Celia and Matsuoka, Yumiko and Tsybovsky, Yaroslav and Baxa, Ulrich and Mullikin, James C. and Subbarao, Kanta and Douek, Daniel C. and Graham, Barney S. and Koup, Richard A. and Ledgerwood, Julie E. and Roederer, Mario and Shapiro, Lawrence and Kwong, Peter D. and Mascola, John R. and McDermott, Adrian B.},
abstractNote = {Antibodies capable of neutralizing divergent influenza A viruses could form the basis of a universal vaccine. Here, from subjects enrolled in an H5N1 DNA/MIV-prime-boost influenza vaccine trial, we sorted hemagglutinin cross-reactive memory B cells and identified three antibody classes, each capable of neutralizing diverse subtypes of group 1 and group 2 influenza A viruses. Co-crystal structures with hemagglutinin revealed that each class utilized characteristic germline genes and convergent sequence motifs to recognize overlapping epitopes in the hemagglutinin stem. All six analyzed subjects had sequences from at least one multidonor class, and—in half the subjects—multidonor-class sequences were recovered from >40% of cross-reactive B cells. By contrast, these multidonor-class sequences were rare in published antibody datasets. Vaccination with a divergent hemagglutinin can thus increase the frequency of B cells encoding broad influenza A-neutralizing antibodies. We propose the sequence signature-quantified prevalence of these B cells as a metric to guide universal influenza A immunization strategies.},
doi = {10.1016/j.cell.2016.06.043},
journal = {Cell},
number = 3,
volume = 166,
place = {United States},
year = {2016},
month = {7}
}

Journal Article:
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https://doi.org/10.1016/j.cell.2016.06.043

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