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primary topic: Enhanced protective efficacy of a thermostable RBD-S2 vaccine formulation against SARS-CoV-2 and its variants

Enhanced protective efficacy of a thermostable RBD-S2 vaccine formulation against SARS-CoV-2 and its variants
type: AcademicArticle
type: Article
abstract: With the rapid emergence of variants of concern (VOC), the efficacy of currently licensed vaccines has reduced drastically. VOC mutations largely occur in the S1 subunit of Spike. The S2 subunit of SARS-CoV-2 is conserved and thus more likely to elicit broadly reactive immune responses that could improve protection. However, the contribution of the S2 subunit in improving the overall efficacy of vaccines remains unclear. Therefore, we designed, and evaluated the immunogenicity and protective potential of a stabilized SARS-CoV-2 Receptor Binding Domain (RBD) fused to a stabilized S2. Immunogens were expressed as soluble proteins with approximately fivefold higher purified yield than the Spike ectodomain and formulated along with Squalene-in-water emulsion (SWE) adjuvant. Immunization with S2 alone failed to elicit a neutralizing immune response, but significantly reduced lung viral titers in mice challenged with the heterologous Beta variant. In hamsters, SWE-formulated RS2 (a genetic fusion of stabilized RBD with S2) showed enhanced immunogenicity and efficacy relative to corresponding RBD and Spike formulations. Despite being based on the ancestral Wuhan strain of SARS-CoV-2, RS2 elicited broad neutralization, including against Omicron variants (BA.1, BA.5 and BF.7), and the clade 1a WIV-1 and SARS-CoV-1 strains. RS2 elicited sera showed enhanced competition with both S2 directed and RBD Class 4 directed broadly neutralizing antibodies, relative to RBD and Spike elicited sera. When lyophilized, RS2 retained antigenicity and immunogenicity even after incubation at 37 °C for a month. The data collectively suggest that the RS2 immunogen is a promising modality to combat SARS-CoV-2 variants.
date: 2023-10-25
volume: 8
issue: 1
status: peerReviewed
status: published
author list: authors
type: EPrint
type: ArticleEPrint
is part of: repository
subject: QR Microbiology

Springer Science and Business Media LLC
type: Organization

NPJ Vaccines
type: Collection

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

Suba Soundarya Sa
type: Person
given name: Suba Soundarya
family name: Sa

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

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

Virginie and Bj Lemoine
type: Person
given name: Virginie and Bj
family name: Lemoine

Nidhi Mittal
type: Person
given name: Nidhi
family name: Mittal

Patrice Dubois
type: Person
given name: Patrice
family name: Dubois

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

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

Harry Kleanthous
type: Person
given name: Harry
family name: Kleanthous

HTML Summary of #3375 Enhanced protective efficacy of a thermostable RBD-S2 vaccine formulation against SARS-CoV-2 and its variants
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primary topic: Enhanced protective efficacy of a thermostable RBD-S2 vaccine formulation against SARS-CoV-2 and its variants

QR Microbiology
type: Concept