%A Simran Srivastava
%A Sahil Kumar
%A Suman Mishra
%A Raju S Rajmani
%A Randhir Singh
%A Somnath Dutta
%A Rajesh Prakash Ringe
%A Raghavan Varadarajan
%O Copyright of this article belongs to ACS.
%J ACS Infect. Dis.
%T Development of a thermostable and broadly neutralizing pan-sarbecovirus vaccine candidate
%X 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.
%N 1
%K SARS-CoV-2; coronavirus; efficacy; lyophilized; preparedness; protein-subunit; thermostability; yield
%P 104-118
%V 12
%D 2026
%I American Chemical Society (ACS)
%L open3207