TY  - JOUR
N1  - Copyright of this article belongs to ACS.
ID  - open3207
UR  - http://crdd.osdd.net/open/3207/
IS  - 1
A1  - Srivastava, Simran
A1  - Kumar, Sahil
A1  - Mishra, Suman
A1  - Rajmani, Raju S
A1  - Singh, Randhir
A1  - Dutta, Somnath
A1  - Ringe, Rajesh Prakash
A1  - Varadarajan, Raghavan
Y1  - 2026/01//
N2  - 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.
PB  - American Chemical Society (ACS)
JF  - ACS Infect. Dis.
VL  - 12
KW  - SARS-CoV-2; coronavirus; efficacy; lyophilized; preparedness; protein-subunit; thermostability; yield
TI  - Development of a thermostable and broadly neutralizing pan-sarbecovirus vaccine candidate
SP  - 104
EP  - 118
ER  -