Department of Microbiology, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA 19104, USA.
Department of Molecular Medicine and Department of Immunology and Microbiology, Scripps Research Institute, La Jolla, CA 92037, USA.
Cell Rep. 2022 May 31;39(9):110897. doi: 10.1016/j.celrep.2022.110897.
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.
在 COVID-19 大流行初期，流感病毒的传播水平非常低，而且人们对这些病毒的群体免疫力较低。一种具有相对于 2021-22 年 H3N2 疫苗株发生若干突变的血凝素（HA）的 H3N2 株（3C.2a1b.2a2）主导了 2021-22 年北半球流感季节。在这里，我们表明这些突变中的一个消除了 HA 上的一个关键糖基化位点，并改变了唾液酸结合。通过糖基化芯片分析，我们表明 3C.2a1b.2a2 H3 保持与扩展的双天线唾液酸苷的结合，并在人呼吸道细胞中以高滴度复制。我们发现，由 2021-22 年北半球流感疫苗诱导的抗体对 3C.2a1b.2a2 H3N2 株的中和效果不佳。综上所述，这些数据表明 3C.2a1b.2a2 H3N2 病毒能够在人类细胞中高效复制，并逃避疫苗诱导的抗体。
