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Influenza viruses circulated at very low levels during the beginning of the COVID-19 pandemic, and population immunity against these viruses is low. An H3N2 strain (3C.2a1b.2a2) with a hemagglutinin (HA) that has several substitutions relative to the 2021-22 H3N2 vaccine strain is dominating the 2021-22 Northern Hemisphere influenza season. Here, we show that one of these substitutions eliminates a key glycosylation site on HA and alters sialic acid binding. Using glycan array profiling, we show that the 3C.2a1b.2a2 H3 maintains binding to an extended biantennary sialoside and replicates to high titers in human airway cells. We find that antibodies elicited by the 2021-22 Northern Hemisphere influenza vaccine poorly neutralize the 3C.2a1b.2a2 H3N2 strain. Together, these data indicate that 3C.2a1b.2a2 H3N2 viruses efficiently replicate in human cells and escape vaccine-elicited antibodies. Copyright © 2022 The Authors. Published by Elsevier Inc. All rights reserved.


Marcus J Bolton, Jordan T Ort, Ryan McBride, Nicholas J Swanson, Jo Wilson, Moses Awofolaju, Colleen Furey, Allison R Greenplate, Elizabeth M Drapeau, Andrew Pekosz, James C Paulson, Scott E Hensley. Antigenic and virological properties of an H3N2 variant that continues to dominate the 2021-22 Northern Hemisphere influenza season. Cell reports. 2022 May 31;39(9):110897

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PMID: 35649381

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