Antigenic Drift of Influenza A(H7N9) Virus Hemagglutinin. (5th July 2018)

• Record Type: Journal Article
• Authors: Ning, Tingting; Nie, Jianhui; Huang, Weijin; Li, Changgui; Li, Xuguang; Liu, Qiang; Zhao, Hui; Wang, Youchun
• Is Part Of: Journal of infectious diseases. Volume 219:Number 1(2019)
• Page Start: 19
• Page End: 25
• Publication Date: 2018-07-05
• Subjects: H7N9 -- hemagglutinin -- antigenic drift -- amino acid substitutions -- vaccine; Communicable diseases -- Periodicals; Diseases -- Causes and theories of causation -- Periodicals; Medicine -- Periodicals; Communicable Diseases -- Periodicals; Electronic journals; 616.9
• DOI: 10.1093/infdis/jiy408
• Languages: English
• ISSNs: 0022-1899

Abstract

Abstract: 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. Abstract : Influenza A(H7N9) virus evolved rapidly in recent years, and the A143V/R148K mutant has become the most dominant variant. However, this mutant demonstrated a 10-fold reduction in its reactivity to antisera from influenza A/Anhui/1/2013(H7N9) virus. Therefore, enhanced surveillance of antigenic change of influenza A(H7N9) virus is urgently needed.