» Articles » PMID: 39960410

A Single Mutation at Position 214 of Influenza B Hemagglutinin Enhances Cross-neutralization

Overview
Date 2025 Feb 17
PMID 39960410
Authors
Affiliations
Soon will be listed here.
Abstract

High variability of influenza B virus (IBV) hemagglutinin (HA) impairs the cross- neutralization ability of vaccines, leading to reduce efficacy. We identified significant differences in cross-neutralization between IBV strains B/Wyoming/06/2014 and B/Brisbane/60/2008, which differ in only three amino acid residues. The 214 T point mutation was found to dramatically enhance cross-neutralization (>10-fold). Antibody-based reverse validation also revealed that this mutation significantly increased the neutralization capacity (500-62,500-fold). Furthermore, monitoring revealed that the mutation rate at this site has reached its highest level in nearly 20 years, with a prevalence exceeding 80% in sequences submitted from certain regions. Our findings provide new evidence for the selection of vaccine strains with improved cross- neutralization effects, which will aid the development of broad-spectrum vaccines by modifying minimal antigenic epitopes.

References
1.
Shen C, Chen J, Li R, Zhang M, Wang G, Stegalkina S . A multimechanistic antibody targeting the receptor binding site potently cross-protects against influenza B viruses. Sci Transl Med. 2017; 9(412). DOI: 10.1126/scitranslmed.aam5752. View

2.
Van Poucke S, Doedt J, Baumann J, Qiu Y, Matrosovich T, Klenk H . Role of Substitutions in the Hemagglutinin in the Emergence of the 1968 Pandemic Influenza Virus. J Virol. 2015; 89(23):12211-6. PMC: 4645308. DOI: 10.1128/JVI.01292-15. View

3.
Guthmiller J, Han J, Utset H, Li L, Lan L, Henry C . Broadly neutralizing antibodies target a haemagglutinin anchor epitope. Nature. 2021; 602(7896):314-320. PMC: 8828479. DOI: 10.1038/s41586-021-04356-8. View

4.
Wang Q, Cheng F, Lu M, Tian X, Ma J . Crystal structure of unliganded influenza B virus hemagglutinin. J Virol. 2008; 82(6):3011-20. PMC: 2259021. DOI: 10.1128/JVI.02477-07. View

5.
Corti D, Voss J, Gamblin S, Codoni G, Macagno A, Jarrossay D . A neutralizing antibody selected from plasma cells that binds to group 1 and group 2 influenza A hemagglutinins. Science. 2011; 333(6044):850-6. DOI: 10.1126/science.1205669. View