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primary topic: Mammalian cell expressed recombinant trimeric spike protein is a potent vaccine antigen and confers near-complete protection against SARS-CoV-2 infection in Hamster

Mammalian cell expressed recombinant trimeric spike protein is a potent vaccine antigen and confers near-complete protection against SARS-CoV-2 infection in Hamster
type: AcademicArticle
type: Article
abstract: Numerous vaccine candidates have emerged in the fight against SARS-CoV-2, yet the challenges posed by viral evolution and the evasion of vaccine-induced immunity persist. The development of broadly protective vaccines is essential in countering the threat posed by variants of concern (VoC) capable of eluding existing vaccine defenses. Among the diverse SARS-CoV-2 vaccine candidates, detailed characterization of those based on the expression of the entire spike protein in mammalian cells have been limited. In our study, we engineered a recombinant prefusion-stabilized trimeric spike protein antigen, IMT-CVAX, encoded by the IMT-C20 gene. This antigen was expressed utilizing a suspension mammalian cell line (CHO-S). The establishment of a stable cell line expressing IMT-CVAX involved the integration of the gene into the CHO genome, followed by the expression, purification, and characterization of the protein. To gauge the vaccine potential of adjuvanted IMT-CVAX, we conducted assessments in small animals. Analyses of blood collected from immunized animals included measurements of anti-spike IgG, SARS-CoV-2 neutralization, and responses from GC-B and Tfh cells. Furthermore, the protective efficacy of IMT-CVAX was evaluated using a Hamster challenge model. Our findings indicate that adjuvanted IMT-CVAX elicits an excellent immune response in both mice and hamsters. Notably, sera from animals immunized with IMT-CVAX effectively neutralize a diverse range of SARS-CoV-2 variants. Moreover, IMT-CVAX immunization conferred complete protection to hamsters against SARS-CoV-2 infection. In hACE2 transgenic mice, IMT-CVAX vaccination induced a robust response from GC-B and Tfh cells. Based on our preclinical model assessments, adjuvanted IMT-CVAX emerges as a highly efficacious vaccine candidate. This protein-subunit-based vaccine exhibits promise for clinical development, offering an affordable solution for both primary and heterologous immunization against SARS-CoV-2 variants.
date: 2024-08
volume: 42
issue: 20
author list: authors
type: EPrint
type: ArticleEPrint
is part of: repository

Elsevier BV
type: Organization

Vaccine
type: Collection

Ashwani K Bhardwaj
type: Person
given name: Ashwani K
family name: Bhardwaj

Ravi P N Mishra
type: Person
given name: Ravi P N
family name: Mishra

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

Shashank Tripathi
type: Person
given name: Shashank
family name: Tripathi

Dhananjay S Mankotia
type: Person
given name: Dhananjay S
family name: Mankotia

Jitender} and Vikram Kumar, B and Singh, Sneha and Verma, Geetik
type: Person
family name: Jitender} and Vikram Kumar, B and Singh, Sneha and Verma, Geetik

Nimesh Gupta
type: Person
given name: Nimesh
family name: Gupta

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primary topic: Mammalian cell expressed recombinant trimeric spike protein is a potent vaccine antigen and confers near-complete protection against SARS-CoV-2 infection in Hamster