tetano
Editor, Senior Moderator
J Virol
. 2020 Aug 12;JVI.00667-20.
doi: 10.1128/JVI.00667-20. Online ahead of print.
L226Q mutation on influenza H7N9 virus hemagglutinin increases receptor-binding avidity and leads to biased antigenicity evaluation
Yang Wang[SUP] 1 [/SUP], Yunhua Lv[SUP] 1 [/SUP], Xuefeng Niu[SUP] 1 [/SUP], Ji Dong[SUP] 1 [/SUP], Pei Feng[SUP] 1 [/SUP], Qinming Li[SUP] 1 [/SUP], Wei Xu[SUP] 1 [/SUP], Jiashun Li[SUP] 1 [/SUP], Chufang Li[SUP] 1 [/SUP], Jiahui Li[SUP] 1 [/SUP], Jia Luo[SUP] 2 [/SUP], Zhixia Li[SUP] 2 [/SUP], Yichu Liu[SUP] 2 [/SUP], Yee-Joo Tan[SUP] 3 [/SUP], Weiqi Pan[SUP] 4 [/SUP], Ling Chen[SUP] 4 [/SUP]
Affiliations
Abstract
Since the first outbreak in 2013, the influenza A (H7N9) virus has continued emerging and caused over five epidemic waves. Suspected antigenic changes of the H7N9 virus based on hemagglutination inhibition (HI) assay during the fifth outbreak have prompted the update of H7N9 candidate vaccine viruses (CVVs). In this study, we comprehensively compared the serological cross-reactivity induced by the hemagglutinins (HAs) of the earlier CVV A/Anhui/1/2013 (H7/AH13) and the updated A/Guangdong/17SF003/2016 (H7/GD16). We found that although H7/GD16 showed poor HI cross-reactivity to immune sera from mice and rhesus macaques vaccinated with either H7/AH13 or H7/GD16, the cross-reactive neutralizing antibodies between H7/AH13 and H7/GD16 were comparably high. Passive transfer of H7/AH13 immune sera also provided complete protection against the lethal challenge of H7N9/GD16 virus in mice. Analysis of amino acid mutations in the HAs between H7/AH13 and H7/GD16 revealed that L226Q substitution increases the HA binding avidity to sialic acid receptors on red blood cells, leading to decreased HI titers against viruses containing HA Q226 and thus resulted in a biased antigenic evaluation based on HI assay. These results suggest that amino acids located in the receptor-binding site could mislead the evaluation of antigenic variation by solely impact on the receptor-binding avidity to red blood cells without genuine contribution to antigenic drift. Our study highlights that viral receptor-binding avidity and combination of multiple serological assays should be taken into consideration in evaluating and selecting a candidate vaccine virus of H7N9 and other subtypes of influenza viruses.IMPORTANCE 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 HI assay. Other serological assays, such as MN assay, should be considered as a complementary indicator for analysis of antigenic variation and selection of influenza CVVs.
. 2020 Aug 12;JVI.00667-20.
doi: 10.1128/JVI.00667-20. Online ahead of print.
L226Q mutation on influenza H7N9 virus hemagglutinin increases receptor-binding avidity and leads to biased antigenicity evaluation
Yang Wang[SUP] 1 [/SUP], Yunhua Lv[SUP] 1 [/SUP], Xuefeng Niu[SUP] 1 [/SUP], Ji Dong[SUP] 1 [/SUP], Pei Feng[SUP] 1 [/SUP], Qinming Li[SUP] 1 [/SUP], Wei Xu[SUP] 1 [/SUP], Jiashun Li[SUP] 1 [/SUP], Chufang Li[SUP] 1 [/SUP], Jiahui Li[SUP] 1 [/SUP], Jia Luo[SUP] 2 [/SUP], Zhixia Li[SUP] 2 [/SUP], Yichu Liu[SUP] 2 [/SUP], Yee-Joo Tan[SUP] 3 [/SUP], Weiqi Pan[SUP] 4 [/SUP], Ling Chen[SUP] 4 [/SUP]
Affiliations
- PMID: 32796071
- DOI: 10.1128/JVI.00667-20
Abstract
Since the first outbreak in 2013, the influenza A (H7N9) virus has continued emerging and caused over five epidemic waves. Suspected antigenic changes of the H7N9 virus based on hemagglutination inhibition (HI) assay during the fifth outbreak have prompted the update of H7N9 candidate vaccine viruses (CVVs). In this study, we comprehensively compared the serological cross-reactivity induced by the hemagglutinins (HAs) of the earlier CVV A/Anhui/1/2013 (H7/AH13) and the updated A/Guangdong/17SF003/2016 (H7/GD16). We found that although H7/GD16 showed poor HI cross-reactivity to immune sera from mice and rhesus macaques vaccinated with either H7/AH13 or H7/GD16, the cross-reactive neutralizing antibodies between H7/AH13 and H7/GD16 were comparably high. Passive transfer of H7/AH13 immune sera also provided complete protection against the lethal challenge of H7N9/GD16 virus in mice. Analysis of amino acid mutations in the HAs between H7/AH13 and H7/GD16 revealed that L226Q substitution increases the HA binding avidity to sialic acid receptors on red blood cells, leading to decreased HI titers against viruses containing HA Q226 and thus resulted in a biased antigenic evaluation based on HI assay. These results suggest that amino acids located in the receptor-binding site could mislead the evaluation of antigenic variation by solely impact on the receptor-binding avidity to red blood cells without genuine contribution to antigenic drift. Our study highlights that viral receptor-binding avidity and combination of multiple serological assays should be taken into consideration in evaluating and selecting a candidate vaccine virus of H7N9 and other subtypes of influenza viruses.IMPORTANCE 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 HI assay. Other serological assays, such as MN assay, should be considered as a complementary indicator for analysis of antigenic variation and selection of influenza CVVs.