A pan-influenza antibody inhibiting neuraminidase via receptor mimicry

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.

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March 2021
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Sample size N/A Data exclusions N/A Replication Experimental assays were performed at least in two independent replicates. Each replicate was performed with 2, 3, or more technical repeats according to or exceeding standards in the field. We conducted all neutralization and antibody functional assays in biological duplicate, triplicate, or more, as indicated in relevant figure legends. In all cases, representative figure displays were appropriately indicated.
Randomization Randomization was not a relevant feature as we were applying a uniform set of techniques across a panel of monoclonal antibodies.

Blinding
Blinding was not a relevant feature as we were applying a uniform set of techniques across a panel of monoclonal antibodies and tests were repeated two or more times by different individuals.
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Validation
Target validation of this antibody was performed by multiple binding and NAI assays. In addition cryoEM structures were determined. Reactivity of commercial antibodies was based on the information on manufacturer's homepages. Wild animals

Eukaryotic cell lines
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Flow Cytometry
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