L226Q Mutation on Influenza H7N9 Virus Hemagglutinin Increases Receptor-Binding Avidity and Leads to Biased Antigenicity Evaluation
Yang Wang, Yunhua Lv, Xuefeng Niu, Ji Dong, Pei Feng, Qinming Li, Wei Xü, Jiashun Li, Chufang Li, Jiahui Li, Jia Luo, Zhixia Li, Yichu Liu, Yee‐Joo Tan, Weiqi Pan, Ling Chen
Abstract
The HI assay is a standard method for profiling the antigenic characterization of influenza viruses. Suspected antigenic changes based on HI divergency in H7N9 viruses during the 2016-2017 wave prompted the recommendation of new H7N9 candidate vaccine viruses (CVVs). In this study, we found that the L226Q substitution in HA of A/Guangdong/17SF003/2016 (H7/GD16) increased the viral receptor-binding avidity to red blood cells with no impact on the antigenicity of H7N9 virus. Although immune sera raised by an earlier vaccine strain (H7/AH13) showed poor HI titers against H7/GD16, the H7/AH13 immune sera had potent cross-neutralizing antibody titers against H7/GD16 and could provide complete passive protection against H7N9/GD16 virus challenge in mice. Our study highlights that receptor-binding avidity might lead to biased antigenic evaluation by using the HI assay. Other serological assays, such as the microneutralization (MN) assay, should be considered a complementary indicator for analysis of antigenic variation and selection of influenza CVVs.