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A trimer ancestral spike-based mRNA vaccine confers cross-generational protection against SADS-CoV

Year: 2025
Type: article
Abstract: The emergence of coronavirus variants that evade vaccine protection poses a serious threat to both human health and animal husbandry, including the novel SADS-CoV, an emerging bat-derived coronavirus. Herein, we introduce a "phylogenetic antigen reconstruction" strategy to design a trimeric ancestral spike (tAS) antigen sequence based on evolutionary spike protein analysis. Delivered via nucleoside-modified mRNA-LNP, the tAS mRNA vaccine induced robust and broad-spectrum immunity in mice and sows, conferring complete protection against lethal SADS-CoV challenges in their F1 offspring. Actively immunized piglets also exhibited full resistance to fatal infection. Importantly, the vaccine-elicited antibodies indicated efficient species cross-reactivity blocking SADS-CoV replication in human, monkey-derived cells, and chicken primary cells, and maintained efficacy for 140 days. This study highlights the potential of integrating ancestral antigen design with mRNA-LNP technology to address coronavirus evolution, offering a scalable solution for livestock protection and proactive control of emerging zoonotic coronaviruses.
DOI: 10.1186/s12951-025-03767-3
Authors: Teng Zhang, Jiale Yao, Xinchun Guo, Chaoliang Leng, Saige Liu, Yaxin Chen, Jucai Wang, Mengsi Sun, Hongfu Ma, Longfa Li, Kankan Yang, Yong Wang, Gaiping Zhang, Lunguang Yao
Institutions: Nanyang Normal University, Henan Agricultural University, Luoyang Normal University, Shenzhen Bay Laboratory, Anhui Agricultural University, Zhengzhou University, Henan Academy of Agricultural Sciences, Yangzhou University
Language: English
Field: Medicine
Open Access status: gold
Estimated APC paid: $3,790
OpenAlex ID: W4415834326
FWCI: 0.709
Cites: 56
Cited by: 1
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