biostudies-literatureUnknown15(1)Yang YThe 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 significanEmerging microbes & infections2631206https://www.ebi.ac.uk/biostudies/studies/S-EPMC12927409biostudies-literatureReceptor binding domain-independent pancoronavirus vaccine design by fusion of conserved T/B Epitopes.PMC12927409Hong MYao JLu XDing CLi EXing YHe HJin TFeng FWang JYe XYang YTan WCheng QHuang XZhao GShang YChen YZou RLi BChiu SHuang BTang YTong DfalseReceptor binding domain-independent pancoronavirus vaccine design by fusion of conserved T/B Epitopes.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 significan2026-01-01T00:00:00Z2026 Dec2026-07-16T18:30:44.043Z2026-07-11T03:08:37.337ZS-EPMC129274094167210310.1080/22221751.2026.2631206