First exposure to the pandemic H1N1 virus induced broadly neutralizing antibodies targeting hemagglutinin head epitopes.

Autor:	Guthmiller JJ; Department of Medicine, Section of Rheumatology, University of Chicago, Chicago, IL 60637, USA. jguthmiller@uchicago.edu andrew@scripps.edu wilsonp@uchicago.edu., Han J; Department of Integrative Structural and Computational Biology, The Scripps Research Institute, La Jolla, CA 92037, USA., Li L; Department of Medicine, Section of Rheumatology, University of Chicago, Chicago, IL 60637, USA., Freyn AW; Department of Microbiology, Icahn School of Medicine at Mount Sinai, New York, NY 10029, USA., Liu STH; Department of Microbiology, Icahn School of Medicine at Mount Sinai, New York, NY 10029, USA., Stovicek O; Department of Medicine, Section of Rheumatology, University of Chicago, Chicago, IL 60637, USA., Stamper CT; Committee on Immunology, University of Chicago, Chicago, IL 60637, USA., Dugan HL; Committee on Immunology, University of Chicago, Chicago, IL 60637, USA., Tepora ME; Department of Medicine, Section of Rheumatology, University of Chicago, Chicago, IL 60637, USA., Utset HA; Department of Medicine, Section of Rheumatology, University of Chicago, Chicago, IL 60637, USA., Bitar DJ; Department of Medicine, Section of Rheumatology, University of Chicago, Chicago, IL 60637, USA., Hamel NJ; Department of Medicine, Section of Rheumatology, University of Chicago, Chicago, IL 60637, USA., Changrob S; Department of Medicine, Section of Rheumatology, University of Chicago, Chicago, IL 60637, USA., Zheng NY; Department of Medicine, Section of Rheumatology, University of Chicago, Chicago, IL 60637, USA., Huang M; Department of Medicine, Section of Rheumatology, University of Chicago, Chicago, IL 60637, USA., Krammer F; Department of Microbiology, Icahn School of Medicine at Mount Sinai, New York, NY 10029, USA., Nachbagauer R; Department of Microbiology, Icahn School of Medicine at Mount Sinai, New York, NY 10029, USA., Palese P; Department of Microbiology, Icahn School of Medicine at Mount Sinai, New York, NY 10029, USA.; Department of Medicine, Icahn School of Medicine at Mount Sinai, New York, NY 10029, USA., Ward AB; Department of Integrative Structural and Computational Biology, The Scripps Research Institute, La Jolla, CA 92037, USA. jguthmiller@uchicago.edu andrew@scripps.edu wilsonp@uchicago.edu., Wilson PC; Department of Medicine, Section of Rheumatology, University of Chicago, Chicago, IL 60637, USA. jguthmiller@uchicago.edu andrew@scripps.edu wilsonp@uchicago.edu.; Committee on Immunology, University of Chicago, Chicago, IL 60637, USA.
Jazyk:	angličtina
Zdroj:	Science translational medicine [Sci Transl Med] 2021 Jun 02; Vol. 13 (596).
DOI:	10.1126/scitranslmed.abg4535
Abstrakt:	Broadly neutralizing antibodies are critical for protection against both drifted and shifted influenza viruses. Here, we reveal that first exposure to the 2009 pandemic H1N1 influenza virus recalls memory B cells that are specific to the conserved receptor-binding site (RBS) or lateral patch epitopes of the hemagglutinin (HA) head domain. Monoclonal antibodies (mAbs) generated against these epitopes are broadly neutralizing against H1N1 viruses spanning 40 years of viral evolution and provide potent protection in vivo. Lateral patch-targeting antibodies demonstrated near universal binding to H1 viruses, and RBS-binding antibodies commonly cross-reacted with H3N2 viruses and influenza B viruses. Lateral patch-targeting mAbs were restricted to expressing the variable heavy-chain gene VH3-23 with or without the variable kappa-chain gene VK1-33 and often had a Y-x-R motif within the heavy-chain complementarity determining region 3 to make key contacts with HA. Moreover, lateral patch antibodies that used both VH3-23 and VK1-33 maintained neutralizing capability with recent pH1N1 strains that acquired mutations near the lateral patch. RBS-binding mAbs used a diverse repertoire but targeted the RBS epitope similarly and made extensive contacts with the major antigenic site Sb. Together, our data indicate that RBS- and lateral patch-targeting clones are abundant within the human memory B cell pool, and universal vaccine strategies should aim to drive antibodies against both conserved head and stalk epitopes. (Copyright © 2021 The Authors, some rights reserved; exclusive licensee American Association for the Advancement of Science. No claim to original U.S. Government Works.)
Databáze:	MEDLINE
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