A glycosylation-associated hemagglutinin substitution improves the breadth of an influenza B mRNA vaccine

Abstract

IntroductionInfluenza B virus is an important cause of seasonal influenza, with its contribution varying across regions and seasons. Historically, influenza B viruses have been classified into two major lineages: B/Victoria (BV) and B/Yamagata. No naturally circulating B/Yamagata-lineage viruses have been confirmed after March 2020, making protection against BV the current priority of influenza B vaccination. In our previous study, we demonstrated that the T214A mutation significantly alters the cross-neutralization capacity of this antigen, potentially through altered glycosylation. Notably, the WHO-recommended vaccine strain for the season, B/Austria/1359417/2021 (BV21), lacked the relevant glycosylation position.MethodsWe used an mRNA platform to compare the cross-subclade protection provided by B/Wyoming/06/2014 (BW06) and BV21 within the B/Victoria lineage. We also introduced the D212N substitution into BV21 as a minimal antigenic modification.ResultsThe D212N substitution restored the glycosylation motif in BV21 and enhanced cross-neutralizing responses against the tested heterologous strains. Mice immunized with a high dose of the D212N-modified vaccine showed 100% survival following challenge with the tested viruses from different subclades.DiscussionOur findings provide valuable insights for the development of broadly protective influenza B vaccines.

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BibTeX RIS

BibTeX

@article{cheng2026glycosylationassociated,
  title = {{A glycosylation-associated hemagglutinin substitution improves the breadth of an influenza B mRNA vaccine}},
  author = {Ziqi Cheng and Yeqing Sun and Yunbo Bai and Lan Wang and Chenyan Zhao},
  journal = {Frontiers in Microbiology},
  year = {2026},
  month = nov,
  doi = {10.3389/fmicb.2026.2002454},
  url = {https://www.frontiersin.org/articles/10.3389/fmicb.2026.2002454},
  note = {CC BY 4.0},
}

RIS

TY  - JOUR
TI  - A glycosylation-associated hemagglutinin substitution improves the breadth of an influenza B mRNA vaccine
AU  - Ziqi Cheng
AU  - Yeqing Sun
AU  - Yunbo Bai
AU  - Lan Wang
AU  - Chenyan Zhao
PY  - 2026
DA  - 2026/11/06
JO  - Frontiers in Microbiology
DO  - 10.3389/fmicb.2026.2002454
UR  - https://www.frontiersin.org/articles/10.3389/fmicb.2026.2002454
AB  - IntroductionInfluenza B virus is an important cause of seasonal influenza, with its contribution varying across regions and seasons. Historically, influenza B viruses have been classified into two major lineages: B/Victoria (BV) and B/Yamagata. No naturally circulating B/Yamagata-lineage viruses have been confirmed after March 2020, making protection against BV the current priority of influenza B vaccination. In our previous study, we demonstrated that the T214A mutation significantly alters the cross-neutralization capacity of this antigen, potentially through altered glycosylation. Notably, the WHO-recommended vaccine strain for the season, B/Austria/1359417/2021 (BV21), lacked the relevant glycosylation position.MethodsWe used an mRNA platform to compare the cross-subclade protection provided by B/Wyoming/06/2014 (BW06) and BV21 within the B/Victoria lineage. We also introduced the D212N substitution into BV21 as a minimal antigenic modification.ResultsThe D212N substitution restored the glycosylation motif in BV21 and enhanced cross-neutralizing responses against the tested heterologous strains. Mice immunized with a high dose of the D212N-modified vaccine showed 100% survival following challenge with the tested viruses from different subclades.DiscussionOur findings provide valuable insights for the development of broadly protective influenza B vaccines.
SN  - 1664-302X
ER  -

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