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A pan-influenza antibody inhibiting neuraminidase via receptor mimicry.

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Momont, Corey 
Dang, Ha V 
Zatta, Fabrizia 
Hauser, Kevin 
Wang, Caihong 


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.


Acknowledgements: We thank NanoImaging Services for some of the Cryo-EM data collection and processing; S. A. Kristian and R. Ray (GSK) for their critical reading and scientific insights; the NIBSC and IRR for providing seasonal influenza viruses; and X. Yang, D. E. Root and O. Bare at the Genetic Perturbation Platform (GPP) of the Broad Institute of MIT and Harvard for assistance with the deep mutational scanning library construction, sequencing and variant calling.


Animals, Humans, Mice, Antibodies, Monoclonal, Antibodies, Viral, Antibody Specificity, Arginine, Catalytic Domain, Hemagglutinins, Viral, Influenza A virus, Influenza A Virus, H3N2 Subtype, Influenza B virus, Influenza Vaccines, Influenza, Human, Neuraminidase, Orthomyxoviridae Infections, Seasons, Sialic Acids, Molecular Mimicry

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Springer Science and Business Media LLC