tetano
Editor, Senior Moderator
NPJ Vaccines
. 2026 Feb 20.
doi: 10.1038/s41541-026-01403-1. Online ahead of print.
A modular three in one mucosal vaccine against three antigenic clusters of ACE2 using sarbecoviruses
Lin Liu[SUP] #[/SUP][SUP] 1 [/SUP], Haofeng Lin[SUP] #[/SUP][SUP] 2 [/SUP], Min Li[SUP] #[/SUP][SUP] 3 [/SUP], Xian Li[SUP] 3 [/SUP], Shasha Wang[SUP] 3 [/SUP], Mengxin Xu[SUP] 1 [/SUP], Shuning Liu[SUP] 1 [/SUP], Yunqi Hu[SUP] 1 [/SUP], Mei-Qin Liu[SUP] 4 [/SUP], Zhixiang Huang[SUP] 5 [/SUP], Zhen Zhang[SUP] 5 [/SUP], Ke Lan[SUP] 5 [/SUP], Yu Chen[SUP] 5 [/SUP], Huimin Yan[SUP] 3 [/SUP], Li Zhou[SUP] 6 [/SUP], Qingguo Wu[SUP] 7 [/SUP], Yao-Qing Chen[SUP] 8 [/SUP], Jingyi Yang[SUP] 9 [/SUP]
Affiliations
The recurrent emergence of ACE2‑using sarbecovirus underscores the need for a broadly protective vaccine. Here, we mapped the antigenic landscape of sarbecovirus receptor-binding domains (RBDs) and identified three distinct clusters. We then engineered a single "three‑in‑one" immunogen, 3Rs-NC, incorporating representative RBDs from each cluster into a single scaffold. Intranasal administration of 3Rs-NC with a flagellin-derived mucosal adjuvant (KFD), which possess excellent safety profile potential for clinical usage, elicited high titers of RBD-specific serum IgG and mucosal IgA, as well as potent neutralizing antibody responses in mice. Furthermore, KFD-adjuvanted 3Rs-NC conferred sustained protection in both the upper and lower respiratory tracts against SARS-CoV-2 Omicron BA.1 and SARS-like coronavirus WIV1. Additionally, 3Rs-NC immunization protected mice from lethal challenge of SARS-like coronavirus rRsSHC014S, with more efficient protection observed in female mice than male mice. This needle-free formulation offers a potent, broad-spectrum vaccine candidate against current and emerging ACE2-using sarbecoviruses, functioning as a modular "three-in-one" vaccine platform ready for rapid deployment in future coronavirus outbreaks.
. 2026 Feb 20.
doi: 10.1038/s41541-026-01403-1. Online ahead of print.
A modular three in one mucosal vaccine against three antigenic clusters of ACE2 using sarbecoviruses
Lin Liu[SUP] #[/SUP][SUP] 1 [/SUP], Haofeng Lin[SUP] #[/SUP][SUP] 2 [/SUP], Min Li[SUP] #[/SUP][SUP] 3 [/SUP], Xian Li[SUP] 3 [/SUP], Shasha Wang[SUP] 3 [/SUP], Mengxin Xu[SUP] 1 [/SUP], Shuning Liu[SUP] 1 [/SUP], Yunqi Hu[SUP] 1 [/SUP], Mei-Qin Liu[SUP] 4 [/SUP], Zhixiang Huang[SUP] 5 [/SUP], Zhen Zhang[SUP] 5 [/SUP], Ke Lan[SUP] 5 [/SUP], Yu Chen[SUP] 5 [/SUP], Huimin Yan[SUP] 3 [/SUP], Li Zhou[SUP] 6 [/SUP], Qingguo Wu[SUP] 7 [/SUP], Yao-Qing Chen[SUP] 8 [/SUP], Jingyi Yang[SUP] 9 [/SUP]
Affiliations
- PMID: 41720818
- DOI: 10.1038/s41541-026-01403-1
The recurrent emergence of ACE2‑using sarbecovirus underscores the need for a broadly protective vaccine. Here, we mapped the antigenic landscape of sarbecovirus receptor-binding domains (RBDs) and identified three distinct clusters. We then engineered a single "three‑in‑one" immunogen, 3Rs-NC, incorporating representative RBDs from each cluster into a single scaffold. Intranasal administration of 3Rs-NC with a flagellin-derived mucosal adjuvant (KFD), which possess excellent safety profile potential for clinical usage, elicited high titers of RBD-specific serum IgG and mucosal IgA, as well as potent neutralizing antibody responses in mice. Furthermore, KFD-adjuvanted 3Rs-NC conferred sustained protection in both the upper and lower respiratory tracts against SARS-CoV-2 Omicron BA.1 and SARS-like coronavirus WIV1. Additionally, 3Rs-NC immunization protected mice from lethal challenge of SARS-like coronavirus rRsSHC014S, with more efficient protection observed in female mice than male mice. This needle-free formulation offers a potent, broad-spectrum vaccine candidate against current and emerging ACE2-using sarbecoviruses, functioning as a modular "three-in-one" vaccine platform ready for rapid deployment in future coronavirus outbreaks.