Broadly neutralizing antibodies target a haemagglutinin anchor epitope.

Autor: Guthmiller JJ; Department of Medicine, Section of Rheumatology, University of Chicago, Chicago, IL, USA. jguthmiller@uchicago.edu., Han J; Department of Integrative Structural and Computational Biology, The Scripps Research Institute, La Jolla, CA, USA., Utset HA; Department of Medicine, Section of Rheumatology, University of Chicago, Chicago, IL, USA., Li L; Department of Medicine, Section of Rheumatology, University of Chicago, Chicago, IL, USA., Lan LY; Committee on Immunology, University of Chicago, Chicago, IL, USA., Henry C; Department of Medicine, Section of Rheumatology, University of Chicago, Chicago, IL, USA.; Moderna Inc., Cambridge, MA, USA., Stamper CT; Committee on Immunology, University of Chicago, Chicago, IL, USA., McMahon M; Department of Microbiology, Icahn School of Medicine at Mount Sinai, New York, NY, USA., O'Dell G; Department of Microbiology, Icahn School of Medicine at Mount Sinai, New York, NY, USA., Fernández-Quintero ML; Center for Molecular Biosciences Innsbruck, Department of General, Inorganic and Theoretical Chemistry, University of Innsbruck, Innsbruck, Austria., Freyn AW; Department of Microbiology, Icahn School of Medicine at Mount Sinai, New York, NY, USA.; Moderna Inc., Cambridge, MA, USA., Amanat F; Department of Microbiology, Icahn School of Medicine at Mount Sinai, New York, NY, USA., Stovicek O; Department of Medicine, Section of Rheumatology, University of Chicago, Chicago, IL, USA., Gentles L; Basic Sciences Division, Fred Hutchinson Cancer Research Center, Seattle, WA, USA.; Department of Microbiology, University of Washington, Seattle, WA, USA., Richey ST; Department of Integrative Structural and Computational Biology, The Scripps Research Institute, La Jolla, CA, USA., de la Peña AT; Department of Integrative Structural and Computational Biology, The Scripps Research Institute, La Jolla, CA, USA., Rosado V; Department of Microbiology, Icahn School of Medicine at Mount Sinai, New York, NY, USA., Dugan HL; Committee on Immunology, University of Chicago, Chicago, IL, USA., Zheng NY; Department of Medicine, Section of Rheumatology, University of Chicago, Chicago, IL, USA., Tepora ME; Department of Medicine, Section of Rheumatology, University of Chicago, Chicago, IL, USA., Bitar DJ; Department of Medicine, Section of Rheumatology, University of Chicago, Chicago, IL, USA., Changrob S; Department of Medicine, Section of Rheumatology, University of Chicago, Chicago, IL, USA., Strohmeier S; Department of Microbiology, Icahn School of Medicine at Mount Sinai, New York, NY, USA., Huang M; Department of Medicine, Section of Rheumatology, University of Chicago, Chicago, IL, USA., García-Sastre A; Department of Microbiology, Icahn School of Medicine at Mount Sinai, New York, NY, USA.; Department of Medicine, Division of Infectious Diseases, Icahn School of Medicine at Mount Sinai, New York, NY, USA.; Global Health and Emerging Pathogens Institute, Icahn School of Medicine at Mount Sinai, New York, NY, USA.; The Tisch Cancer Center, Icahn School of Medicine at Mount Sinai, New York, NY, USA.; Department of Pathology, Molecular and Cell-Based Medicine, Icahn School of Medicine at Mount Sinai, New York, NY, USA., Liedl KR; Center for Molecular Biosciences Innsbruck, Department of General, Inorganic and Theoretical Chemistry, University of Innsbruck, Innsbruck, Austria., Bloom JD; Basic Sciences Division, Fred Hutchinson Cancer Research Center, Seattle, WA, USA.; Department of Microbiology, University of Washington, Seattle, WA, USA.; Department of Genome Sciences, University of Washington, Seattle, WA, USA.; Howard Hughes Medical Institute, Fred Hutchinson Cancer Research Center, Seattle, WA, USA., Nachbagauer R; Department of Microbiology, Icahn School of Medicine at Mount Sinai, New York, NY, USA.; Moderna Inc., Cambridge, MA, USA., Palese P; Department of Microbiology, Icahn School of Medicine at Mount Sinai, New York, NY, USA.; Department of Medicine, Division of Infectious Diseases, Icahn School of Medicine at Mount Sinai, New York, NY, USA., Krammer F; Department of Microbiology, Icahn School of Medicine at Mount Sinai, New York, NY, USA., Coughlan L; Department of Microbiology and Immunology, University of Maryland School of Medicine, Baltimore, MD, USA.; Center for Vaccine Development and Global Health (CVD), University of Maryland School of Medicine, Baltimore, MD, USA., Ward AB; Department of Integrative Structural and Computational Biology, The Scripps Research Institute, La Jolla, CA, USA. andrew@scripps.edu., Wilson PC; Department of Medicine, Section of Rheumatology, University of Chicago, Chicago, IL, USA. pcw4001@med.cornell.edu.; Committee on Immunology, University of Chicago, Chicago, IL, USA. pcw4001@med.cornell.edu.; Drukier Institute for Children's Health, Department of Pediatrics, Weill Cornell Medicine, New York, NY, USA. pcw4001@med.cornell.edu.
Jazyk: angličtina
Zdroj: Nature [Nature] 2022 Feb; Vol. 602 (7896), pp. 314-320. Date of Electronic Publication: 2021 Dec 23.
DOI: 10.1038/s41586-021-04356-8
Abstrakt: Broadly neutralizing antibodies that target epitopes of haemagglutinin on the influenza virus have the potential to provide near universal protection against influenza virus infection 1 . However, viral mutants that escape broadly neutralizing antibodies have been reported 2,3 . 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 vaccine 4,5 , 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.
(© 2021. The Author(s).)
Databáze: MEDLINE
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