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

Journal Article · · Cell

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.

Research Organization:
Argonne National Laboratory (ANL), Argonne, IL (United States). Advanced Photon Source (APS)
Sponsoring Organization:
National Institutes of Health (NIH); National Institute of Allergy and Infectious Diseases (NIAID); USDOE Office of Science (SC), Basic Energy Sciences (BES)
Contributing Organization:
NISC Comparative Sequencing Program
Grant/Contract Number:
HHSN261200800001E; W-31-109-Eng-38
OSTI ID:
1389087
Alternate ID(s):
OSTI ID: 1314264
Journal Information:
Cell, Journal Name: Cell Vol. 166 Journal Issue: 3; ISSN 0092-8674
Publisher:
ElsevierCopyright Statement
Country of Publication:
United States
Language:
English
Citation Metrics:
Cited by: 216 works
Citation information provided by
Web of Science

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