title: Development of a thermostable and broadly neutralizing pan-sarbecovirus vaccine candidate
creator: Srivastava, Simran
creator: Kumar, Sahil
creator: Mishra, Suman
creator: Rajmani, Raju S
creator: Singh, Randhir
creator: Dutta, Somnath
creator: Ringe, Rajesh Prakash
creator: Varadarajan, Raghavan
subject: QR Microbiology
description: 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.
publisher: American Chemical Society (ACS)
date: 2025-01
type: Article
type: PeerReviewed
identifier:   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  (2025) Development of a thermostable and broadly neutralizing pan-sarbecovirus vaccine candidate.  ACS Infect. Dis., 12 (1).  pp. 104-118.      
relation: http://crdd.osdd.net/open/3282/