A pan-influenza antibody inhibiting neuraminidase via receptor mimicry
Corey Momont,
Ha V. Dang,
Fabrizia Zatta,
Kevin Hauser,
Caihong Wang,
Julia Iulio,
Andrea Minola,
Nadine Czudnochowski,
Anna Marco,
Kaitlin Branch,
David Donermeyer,
Siddhant Vyas,
Alex Chen,
Elena Ferri,
Barbara Guarino,
Abigail E. Powell,
Roberto Spreafico,
Samantha S. Yim,
Dale R. Balce,
Istvan Bartha,
Marcel Meury,
Tristan I. Croll,
David M. Belnap,
Michael A. Schmid,
William Timothy Schaiff,
Jessica L. Miller,
Elisabetta Cameroni,
Amalio Telenti,
Herbert W. Virgin,
Laura E. Rosen,
Lisa A. Purcell,
Antonio Lanzavecchia,
Gyorgy Snell (),
Davide Corti () and
Matteo Samuele Pizzuto ()
Additional contact information
Corey Momont: Vir Biotechnology
Ha V. Dang: Vir Biotechnology
Fabrizia Zatta: Humabs Biomed SA, a subsidiary of Vir Biotechnology
Kevin Hauser: Vir Biotechnology
Caihong Wang: Vir Biotechnology
Julia Iulio: Vir Biotechnology
Andrea Minola: Humabs Biomed SA, a subsidiary of Vir Biotechnology
Nadine Czudnochowski: Vir Biotechnology
Anna Marco: Humabs Biomed SA, a subsidiary of Vir Biotechnology
Kaitlin Branch: Vir Biotechnology
David Donermeyer: Vir Biotechnology
Siddhant Vyas: Vir Biotechnology
Alex Chen: Vir Biotechnology
Elena Ferri: Vir Biotechnology
Barbara Guarino: Humabs Biomed SA, a subsidiary of Vir Biotechnology
Abigail E. Powell: Vir Biotechnology
Roberto Spreafico: Vir Biotechnology
Samantha S. Yim: Vir Biotechnology
Dale R. Balce: Vir Biotechnology
Istvan Bartha: Vir Biotechnology
Marcel Meury: Vir Biotechnology
Tristan I. Croll: University of Cambridge
David M. Belnap: University of Utah
Michael A. Schmid: Humabs Biomed SA, a subsidiary of Vir Biotechnology
William Timothy Schaiff: Vir Biotechnology
Jessica L. Miller: Vir Biotechnology
Elisabetta Cameroni: Humabs Biomed SA, a subsidiary of Vir Biotechnology
Amalio Telenti: Vir Biotechnology
Herbert W. Virgin: Vir Biotechnology
Laura E. Rosen: Vir Biotechnology
Lisa A. Purcell: Vir Biotechnology
Antonio Lanzavecchia: Humabs Biomed SA, a subsidiary of Vir Biotechnology
Gyorgy Snell: Vir Biotechnology
Davide Corti: Humabs Biomed SA, a subsidiary of Vir Biotechnology
Matteo Samuele Pizzuto: Humabs Biomed SA, a subsidiary of Vir Biotechnology
Nature, 2023, vol. 618, issue 7965, 590-597
Abstract:
Abstract Rapidly evolving influenza A viruses (IAVs) and influenza B viruses (IBVs) are major causes of recurrent lower respiratory tract infections. Current influenza vaccines elicit antibodies predominantly to the highly variable head region of haemagglutinin and their effectiveness is limited by viral drift1 and suboptimal immune responses2. Here we describe a neuraminidase-targeting monoclonal antibody, FNI9, that potently inhibits the enzymatic activity of all group 1 and group 2 IAVs, as well as Victoria/2/87-like, Yamagata/16/88-like and ancestral IBVs. FNI9 broadly neutralizes seasonal IAVs and IBVs, including the immune-evading H3N2 strains bearing an N-glycan at position 245, and shows synergistic activity when combined with anti-haemagglutinin stem-directed antibodies. Structural analysis reveals that D107 in the FNI9 heavy chain complementarity-determinant region 3 mimics the interaction of the sialic acid carboxyl group with the three highly conserved arginine residues (R118, R292 and R371) of the neuraminidase catalytic site. FNI9 demonstrates potent prophylactic activity against lethal IAV and IBV infections in mice. The unprecedented breadth and potency of the FNI9 monoclonal antibody supports its development for the prevention of influenza illness by seasonal and pandemic viruses.
Date: 2023
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Persistent link: https://EconPapers.repec.org/RePEc:nat:nature:v:618:y:2023:i:7965:d:10.1038_s41586-023-06136-y
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DOI: 10.1038/s41586-023-06136-y
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