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| Title | Development of a Thermostable and Broadly Neutralizing Pan-Sarbecovirus Vaccine Candidate. |
|---|---|
| Journal, issue, pages | ACS Infect Dis, Vol. 12, Issue 1, Page 104-118, Year 2026 |
| Publish date | Jan 9, 2026 |
Authors | Simran Srivastava / Sahil Kumar / Suman Mishra / Raju S Rajmani / Randhir Singh / Somnath Dutta / Rajesh Prakash Ringe / Raghavan Varadarajan / ![]() |
| PubMed Abstract | Zoonotic spillover of sarbecoviruses to humans resulted in the SARS-CoV-1 outbreak in 2003 and the current COVID-19 pandemic caused by SARS-CoV-2. In both cases, the viral spike protein (S) is the ...Zoonotic spillover of sarbecoviruses to humans resulted in the SARS-CoV-1 outbreak in 2003 and the current COVID-19 pandemic caused by SARS-CoV-2. In both cases, the viral spike protein (S) is the principal target of neutralizing antibodies that prevent infection. Within the spike, the immunodominant receptor-binding domain (RBD) is the primary target of neutralizing antibodies in COVID-19 convalescent sera and vaccine recipients. We have constructed stabilized RBD derivatives of different sarbecoviruses: SARS-CoV-1 (Clade 1a), WIV-1 (Clade 1a), RaTG13 (Clade 1b), RmYN02 (Clade 2), and BtKY72 (Clade 3). Stabilization enhanced yield by 3-23-fold. The RBD derivatives were conformationally intact, as assayed by binding to multiple broadly neutralizing antibodies. The stabilized RBDs show significant enhancement in apparent , exhibit resistance to a 2-h incubation at temperatures up to 60 °C in PBS in contrast to the corresponding WT RBDs, and show prolonged stability of over 15 days at 37 °C after lyophilization. In mice immunizations, both stabilization and trimerization significantly enhanced elicited neutralization titers by ∼100-fold. The stabilized RBD cocktail elicited highly neutralizing titers against both homologous and heterologous pseudoviruses. The immunogenicity of the vaccine formulation was assessed in both naïve and SARS-CoV-2 preimmunized mice, revealing an absence of immune imprinting, thus indicating its suitability for use in future sarbecovirus-origin epidemics or pandemics. |
External links | ACS Infect Dis / PubMed:41436061 / PubMed Central |
| Methods | EM (single particle) |
| Resolution | 4.55 Å |
| Structure data | EMDB-66202, PDB-9wsp: |
| Source |
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Keywords | VIRAL PROTEIN / Spike Protein |
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Severe acute respiratory syndrome coronavirus
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