@article{open3282,
          volume = {12},
          number = {1},
           month = {January},
          author = {Simran Srivastava and Sahil Kumar and Suman Mishra and Raju S Rajmani and Randhir Singh and Somnath Dutta and Rajesh Prakash Ringe and Raghavan Varadarajan},
           title = {Development of a thermostable and broadly neutralizing pan-sarbecovirus vaccine candidate},
       publisher = {American Chemical Society (ACS)},
            year = {2025},
         journal = {ACS Infect. Dis.},
           pages = {104--118},
        keywords = {SARS-CoV-2; coronavirus; efficacy; lyophilized; preparedness; protein-subunit; thermostability; yield},
             url = {http://crdd.osdd.net/open/3282/},
        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 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 {\^A}?C in PBS in contrast to the corresponding WT RBDs, and show prolonged stability of over 15 days at 37 {\^A}?C after lyophilization. In mice immunizations, both stabilization and trimerization significantly enhanced elicited neutralization titers by {\^a}??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{$\backslash$}"{$\backslash$}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.}
}