tetano
Editor, Senior Moderator
J Nanobiotechnology
. 2025 Nov 4;23(1):700.
doi: 10.1186/s12951-025-03767-3. A trimer ancestral spike-based mRNA vaccine confers cross-generational protection against SADS-CoV
Teng Zhang[SUP] #[/SUP][SUP] 1 2 3 [/SUP], Jiale Yao[SUP] #[/SUP][SUP] 1 [/SUP], Xinchun Guo[SUP] 1 [/SUP], Chaoliang Leng[SUP] 1 [/SUP], Saige Liu[SUP] 1 [/SUP], Yaxin Chen[SUP] 1 [/SUP], Jucai Wang[SUP] 4 [/SUP], Mengsi Sun[SUP] 5 [/SUP], Hongfu Ma[SUP] 6 [/SUP], Longfa Li[SUP] 1 [/SUP], Kankan Yang[SUP] 7 [/SUP], Yong Wang[SUP] 8 [/SUP], Gaiping Zhang[SUP] 9 10 11 12 13 [/SUP], Lunguang Yao[SUP] 14 [/SUP]
Affiliations
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 ([SUP]tA[/SUP]S) antigen sequence based on evolutionary spike protein analysis. Delivered via nucleoside-modified mRNA-LNP, the [SUP]tA[/SUP]S 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.
Keywords: Ancestral phylogenetic; SADS-CoV; Spike protein; Trimer mRNA vaccine.
. 2025 Nov 4;23(1):700.
doi: 10.1186/s12951-025-03767-3. A trimer ancestral spike-based mRNA vaccine confers cross-generational protection against SADS-CoV
Teng Zhang[SUP] #[/SUP][SUP] 1 2 3 [/SUP], Jiale Yao[SUP] #[/SUP][SUP] 1 [/SUP], Xinchun Guo[SUP] 1 [/SUP], Chaoliang Leng[SUP] 1 [/SUP], Saige Liu[SUP] 1 [/SUP], Yaxin Chen[SUP] 1 [/SUP], Jucai Wang[SUP] 4 [/SUP], Mengsi Sun[SUP] 5 [/SUP], Hongfu Ma[SUP] 6 [/SUP], Longfa Li[SUP] 1 [/SUP], Kankan Yang[SUP] 7 [/SUP], Yong Wang[SUP] 8 [/SUP], Gaiping Zhang[SUP] 9 10 11 12 13 [/SUP], Lunguang Yao[SUP] 14 [/SUP]
Affiliations
- PMID: 41185028
- PMCID: PMC12584437
- DOI: 10.1186/s12951-025-03767-3
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 ([SUP]tA[/SUP]S) antigen sequence based on evolutionary spike protein analysis. Delivered via nucleoside-modified mRNA-LNP, the [SUP]tA[/SUP]S 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.
Keywords: Ancestral phylogenetic; SADS-CoV; Spike protein; Trimer mRNA vaccine.