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Receptor binding domain-independent pancoronavirus vaccine design by fusion of conserved T/B Epitopes.

Created on 15 Sep 2026

Authors

Yunru Yang, Yetian Chen, Mengyu Hong, Ronghua Zou, Jingxue Yao, Entao Li, Jiayi Wang, Xiaodong Ye, Yixiang Xing, Yangming Tang, Xiaojie Lu, Chengchao Ding, Hongliang He, Dali Tong, Yuhua Shang, Jian Wang, Guangyu Zhao, Xiaoxue Huang, Fuli Feng, Qingyu Cheng, Bofeng Li, Baoying Huang, Wenjie Tan, Sandra Chiu, Tengchuan Jin

Published in

Emerging microbes & infections. Volume 15. Issue 1. Pages 2631206. Epub Feb 20, 2026.

Abstract

The persistent emergence of SARS-CoV-2 variants continues to compromise current vaccine efficacy, driving the development of broad-spectrum coronavirus vaccines to address variant evasion and future outbreaks. To develop a pan-coronavirus vaccine, we identified some conserved T/B epitopes across spike proteins of human-infecting coronaviruses, focusing on two conserved long peptides, VV and VS, which demonstrated broad immunogenicity in PBMCs from COVID-19 convalescent patients. By structurally fusing the VV and VS long peptides with heptad repeat 1/2 (HR1/2) domains from the S2 subunit, we engineered a trimeric immunogen HR1-VV-HR2-VS. This design induced superior cellular and humoral immune responses compared to individual peptide components in immunized mice. The vaccine also significantly reduced viral loads and attenuated lung pathology in mice challenged with HCoV-229E, SARS-CoV-2 prototype strain, and the KP.2 variant, demonstrating cross-protective immunity. Therefore, these results indicated that HR1-VV-HR2-VS vaccine elicits cross-protective immunity, highlighting its potential as a universal coronavirus vaccine. In addition, we developed an innovative peptide vaccine platform based on the HR1-HR2 trimeric structural protein, which serves as a potent polypeptide fusion scaffold to significantly enhance peptide immunogenicity.

PMID:
41672103
Bibliographic data and abstract were imported from PubMed on 15 Sep 2026.

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