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

Autor: Jitender; Vaccine & Biotherapeutics Research Laboratory, CSIR-Institute of Microbial Technology, Chandigarh, India., Vikram Kumar B; Vaccine & Biotherapeutics Research Laboratory, CSIR-Institute of Microbial Technology, Chandigarh, India., Singh S; Vaccine & Biotherapeutics Research Laboratory, CSIR-Institute of Microbial Technology, Chandigarh, India., Verma G; Vaccine & Biotherapeutics Research Laboratory, CSIR-Institute of Microbial Technology, Chandigarh, India., Kumar R; Vaccine & Biotherapeutics Research Laboratory, CSIR-Institute of Microbial Technology, Chandigarh, India., Mishra PM; Vaccine & Biotherapeutics Research Laboratory, CSIR-Institute of Microbial Technology, Chandigarh, India., Kumar S; Vaccine & Biotherapeutics Research Laboratory, CSIR-Institute of Microbial Technology, Chandigarh, India., Nagaraj SK; Centre for Infectious Disease Research, Indian Institute of Science, Bengaluru, India., Nag J; Centre for Infectious Disease Research, Indian Institute of Science, Bengaluru, India., Joy CM; Centre for Infectious Disease Research, Indian Institute of Science, Bengaluru, India., Nikam B; National Institute of Immunology, New Delhi, India., Singh D; National Institute of Immunology, New Delhi, India., Pooja; Vaccine & Biotherapeutics Research Laboratory, CSIR-Institute of Microbial Technology, Chandigarh, India., Kalidas N; Vaccine & Biotherapeutics Research Laboratory, CSIR-Institute of Microbial Technology, Chandigarh, India., Singh S; Vaccine & Biotherapeutics Research Laboratory, CSIR-Institute of Microbial Technology, Chandigarh, India., Mumtaz; Vaccine & Biotherapeutics Research Laboratory, CSIR-Institute of Microbial Technology, Chandigarh, India., Bhardwaj AK; Vaccine & Biotherapeutics Research Laboratory, CSIR-Institute of Microbial Technology, Chandigarh, India., Mankotia DS; Vaccine & Biotherapeutics Research Laboratory, CSIR-Institute of Microbial Technology, Chandigarh, India., Ringe RP; Vaccine & Biotherapeutics Research Laboratory, CSIR-Institute of Microbial Technology, Chandigarh, India., Gupta N; National Institute of Immunology, New Delhi, India., Tripathi S; Centre for Infectious Disease Research, Indian Institute of Science, Bengaluru, India; Microbiology & Cell Biology Department, Indian Institute of Science, Bengaluru, India., Mishra RPN; Vaccine & Biotherapeutics Research Laboratory, CSIR-Institute of Microbial Technology, Chandigarh, India; Academy of Scientific and Innovative Research (AcSIR), Ghaziabad, India. Electronic address: ravi.mishra@imtech.res.in.
Jazyk: angličtina
Zdroj: Vaccine [Vaccine] 2024 Aug 13; Vol. 42 (20), pp. 126099. Date of Electronic Publication: 2024 Jul 08.
DOI: 10.1016/j.vaccine.2024.06.066
Abstrakt: 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 T fh 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 T fh 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.
Competing Interests: Declaration of competing interest The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: Ravi PN Mishra has patent #PROCESS FOR RECOMBINANT PRODUCTION OF SARS-COV-2 SPIKE PROTEIN pending to NA. If there are other authors, they declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper.
(Copyright © 2024. Published by Elsevier Ltd.)
Databáze: MEDLINE
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