http://crdd.osdd.net/open/id/eprint/3487 2026-07-22T01:03:53Z info:eu-repo/semantics/descriptiveMetadata Development of a thermostable and broadly neutralizing pan-sarbecovirus vaccine candidate Srivastava, Simran Kumar, Sahil Mishra, Suman Rajmani, Raju S Singh, Randhir Dutta, Somnath Ringe, Rajesh Prakash Varadarajan, Raghavan QR Microbiology 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 Tm, 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 na\"\ive 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. American Chemical Society (ACS) 2026-01-09 Article PeerReviewed text/html http://crdd.osdd.net/open/3487/1/references.bib https://pmc.ncbi.nlm.nih.gov/articles/PMC12797234/ Srivastava, Simran and Kumar, Sahil and Mishra, Suman and Rajmani, Raju S and Singh, Randhir and Dutta, Somnath and Ringe, Rajesh Prakash and Varadarajan, Raghavan (2026) Development of a thermostable and broadly neutralizing pan-sarbecovirus vaccine candidate. ACS Infect. Dis., 12 (1). pp. 104-118. http://crdd.osdd.net/open/3487/ info:eu-repo/semantics/objectFile info:eu-repo/semantics/humanStartPage