A pan-influenza antibody inhibiting neuraminidase via receptor mimicry.

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.

• Authors: Corey Momont, Ha V Dang, Fabrizia Zatta, Kevin Hauser, Caihong Wang, Julia di Iulio, Andrea Minola, Nadine Czudnochowski, Anna De 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, Matteo Samuele Pizzuto
• Journal: Nature (Nature) Vol. 618 Issue 7965 Pg. 590-597 (Jun 2023) ISSN: 1476-4687 [Electronic] England
• PMID: 37258672 (Publication Type: Journal Article)
• Copyright: © 2023. The Author(s).

Chemical References

• Antibodies, Monoclonal
• Antibodies, Viral
• Arginine
• Hemagglutinins, Viral
• Influenza Vaccines
• Neuraminidase
• Sialic Acids

Topics

• Animals
• Humans
• Mice
• Antibodies, Monoclonal (chemistry, immunology, therapeutic use)
• Antibodies, Viral (chemistry, immunology, therapeutic use)
• Antibody Specificity (immunology)
• Arginine (chemistry)
• Catalytic Domain
• Hemagglutinins, Viral (immunology)
• Influenza A virus (classification, enzymology, immunology)
• Influenza A Virus, H3N2 Subtype (enzymology, immunology)
• Influenza B virus (classification, enzymology, immunology)
• Influenza Vaccines (chemistry, immunology, therapeutic use)
• Influenza, Human (immunology, prevention & control)
• Neuraminidase (antagonists & inhibitors, chemistry, immunology)
• Orthomyxoviridae Infections (immunology, prevention & control)
• Seasons
• Sialic Acids (chemistry)
• Molecular Mimicry