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primary topic: Development of a thermostable and broadly neutralizing pan-sarbecovirus vaccine candidate

Development of a thermostable and broadly neutralizing pan-sarbecovirus vaccine candidate
type: AcademicArticle
type: Article
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 °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 â�¼100-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.
date: 2025-01
volume: 12
issue: 1
status: peerReviewed
status: published
author list: authors
type: EPrint
type: ArticleEPrint
is part of: repository
subject: QR Microbiology

American Chemical Society (ACS)
type: Organization

ACS Infect. Dis.
type: Collection

Rajesh Prakash Ringe
type: Person
given name: Rajesh Prakash
family name: Ringe

Simran Srivastava
type: Person
given name: Simran
family name: Srivastava

Randhir Singh
type: Person
given name: Randhir
family name: Singh

Raju S Rajmani
type: Person
given name: Raju S
family name: Rajmani

Suman Mishra
type: Person
given name: Suman
family name: Mishra

Sahil Kumar
type: Person
given name: Sahil
family name: Kumar

Somnath Dutta
type: Person
given name: Somnath
family name: Dutta

Raghavan Varadarajan
type: Person
given name: Raghavan
family name: Varadarajan

HTML Summary of #3282 Development of a thermostable and broadly neutralizing pan-sarbecovirus vaccine candidate
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primary topic: Development of a thermostable and broadly neutralizing pan-sarbecovirus vaccine candidate

QR Microbiology
type: Concept