Broadly neutralizing antibodies target a haemagglutinin anchor epitope

Jenna J. Guthmiller (), Julianna Han, Henry A. Utset, Lei Li, Linda Yu-Ling Lan, Carole Henry, Christopher T. Stamper, Meagan McMahon, George O’Dell, Monica L. Fernández-Quintero, Alec W. Freyn, Fatima Amanat, Olivia Stovicek, Lauren Gentles, Sara T. Richey, Alba Torrents Peña, Victoria Rosado, Haley L. Dugan, Nai-Ying Zheng, Micah E. Tepora, Dalia J. Bitar, Siriruk Changrob, Shirin Strohmeier, Min Huang, Adolfo García-Sastre, Klaus R. Liedl, Jesse D. Bloom, Raffael Nachbagauer, Peter Palese, Florian Krammer, Lynda Coughlan, Andrew B. Ward () and Patrick C. Wilson ()
Additional contact information
Jenna J. Guthmiller: University of Chicago
Julianna Han: The Scripps Research Institute
Henry A. Utset: University of Chicago
Lei Li: University of Chicago
Linda Yu-Ling Lan: University of Chicago
Carole Henry: University of Chicago
Christopher T. Stamper: University of Chicago
Meagan McMahon: Icahn School of Medicine at Mount Sinai
George O’Dell: Icahn School of Medicine at Mount Sinai
Monica L. Fernández-Quintero: University of Innsbruck
Alec W. Freyn: Icahn School of Medicine at Mount Sinai
Fatima Amanat: Icahn School of Medicine at Mount Sinai
Olivia Stovicek: University of Chicago
Lauren Gentles: Fred Hutchinson Cancer Research Center
Sara T. Richey: The Scripps Research Institute
Alba Torrents Peña: The Scripps Research Institute
Victoria Rosado: Icahn School of Medicine at Mount Sinai
Haley L. Dugan: University of Chicago
Nai-Ying Zheng: University of Chicago
Micah E. Tepora: University of Chicago
Dalia J. Bitar: University of Chicago
Siriruk Changrob: University of Chicago
Shirin Strohmeier: Icahn School of Medicine at Mount Sinai
Min Huang: University of Chicago
Adolfo García-Sastre: Icahn School of Medicine at Mount Sinai
Klaus R. Liedl: University of Innsbruck
Jesse D. Bloom: Fred Hutchinson Cancer Research Center
Raffael Nachbagauer: Icahn School of Medicine at Mount Sinai
Peter Palese: Icahn School of Medicine at Mount Sinai
Florian Krammer: Icahn School of Medicine at Mount Sinai
Lynda Coughlan: University of Maryland School of Medicine
Andrew B. Ward: The Scripps Research Institute
Patrick C. Wilson: University of Chicago

Nature, 2022, vol. 602, issue 7896, 314-320

Abstract: Abstract Broadly neutralizing antibodies that target epitopes of haemagglutinin on the influenza virus have the potential to provide near universal protection against influenza virus infection1. However, viral mutants that escape broadly neutralizing antibodies have been reported2,3. The identification of broadly neutralizing antibody classes that can neutralize viral escape mutants is critical for universal influenza virus vaccine design. Here we report a distinct class of broadly neutralizing antibodies that target a discrete membrane-proximal anchor epitope of the haemagglutinin stalk domain. Anchor epitope-targeting antibodies are broadly neutralizing across H1 viruses and can cross-react with H2 and H5 viruses that are a pandemic threat. Antibodies that target this anchor epitope utilize a highly restricted repertoire, which encodes two public binding motifs that make extensive contacts with conserved residues in the fusion peptide. Moreover, anchor epitope-targeting B cells are common in the human memory B cell repertoire and were recalled in humans by an oil-in-water adjuvanted chimeric haemagglutinin vaccine4,5, which is a potential universal influenza virus vaccine. To maximize protection against seasonal and pandemic influenza viruses, vaccines should aim to boost this previously untapped source of broadly neutralizing antibodies that are widespread in the human memory B cell pool.

Date: 2022
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Citations: View citations in EconPapers (4)

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DOI: 10.1038/s41586-021-04356-8

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