Antigenic Drift of Influenza A(H7N9) Virus Hemagglutinin

被引:29
作者
Ning, Tingting [1 ,3 ]
Nie, Jianhui [1 ]
Huang, Weijin [1 ]
Li, Changgui [2 ]
Li, Xuguang [4 ]
Liu, Qiang [1 ]
Zhao, Hui [2 ]
Wang, Youchun [1 ,3 ]
机构
[1] Natl Inst Food & Drug Control, Div HIV AIDS & Sexually Transmitted Virus Vaccine, Beijing, Peoples R China
[2] Natl Inst Food & Drug Control, Div Resp Virus Vaccines, Beijing, Peoples R China
[3] Peking Union Med Coll, Grad Sch, Beijing, Peoples R China
[4] Hlth Canada, Ctr Biol Evaluat, Biol & Genet Therapies Directorate, Ottawa, ON, Canada
关键词
H7N9; hemagglutinin; antigenic drift; amino acid substitutions; vaccine; AMINO-ACID SUBSTITUTIONS; RECEPTOR-BINDING SITE; MAJOR CAPSID PROTEIN; IDENTIFICATION; EVOLUTION; EPITOPE;
D O I
10.1093/infdis/jiy408
中图分类号
R392 [医学免疫学]; Q939.91 [免疫学];
学科分类号
100102 ;
摘要
Background. Since the emergence of influenza A(H7N9) virus in 2013, there have been 5 waves of influenza A(H7N9) epidemics in China. However, evolution of the hemagglutinin (HA) protein antigenicity has not been systematically investigated. Methods. To better understand how antigenic drift in HA proteins of influenza (A)H7N9 virus occurs, 902 influenza A(H7N9) virus HA protein sequences from a public database were retrieved and analyzed. Fifty-three mutants with single amino acid substitutions in HA protein were introduced into pseudoviruses, and their antigenic characteristics were analyzed using pseudovirus-based assays. Results. The frequencies of 9 mutations incrementally increased over the past 5 years, with mutations identified at multiple sites. While mean neutralization titers of most variants remained unchanged, 3 mutations, A143V, A143T, and R148K, displayed a median 4-fold lower susceptibility to neutralization by antisera against influenza A/Anhui/1/2013(H7N9) virus. Notably, A143V and A143T were located outside the previously reported antigenic sites. The most dominant variant (A143V/R148K) in the most recent season constituted 74.11% of all mutations and demonstrated a 10-fold reduction in its reactivity to influenza A/Anhui/1/2013(H7N9) virus antisera. Importantly, compared with the DNA construct without the corresponding HA protein mutation, DNA vaccine encoding the A143V/R148K mutant induced a 5-fold increase in the neutralizing activity against this circulating virus. Conclusions. An appropriate vaccine strain should be considered in response to increasing antigenic drift in influenza A(H7N9) virus HA protein.
引用
收藏
页码:19 / 25
页数:7
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