Evaluation of safety and immunogenicity of receptor-binding domain-based COVID-19 vaccine (Corbevax) to select the optimum formulation in open-label, multicentre, and randomised phase-1/2 and phase-2 clinical trials.
Covid-19
Protein subunit
Receptor-binding domain
SARS-CoV-2
Spike protein
Vaccine
Journal
EBioMedicine
ISSN: 2352-3964
Titre abrégé: EBioMedicine
Pays: Netherlands
ID NLM: 101647039
Informations de publication
Date de publication:
Sep 2022
Sep 2022
Historique:
received:
10
03
2022
revised:
29
06
2022
accepted:
28
07
2022
pubmed:
16
8
2022
medline:
21
9
2022
entrez:
15
8
2022
Statut:
ppublish
Résumé
We assessed the efficacy of a receptor-binding domain (RBD)-based protein subunit COVID-19 vaccine. A randomised Phase-1/2 trial followed by a Phase-2 trial were conducted to assess the safety and immunogenicity of the COVID-19 vaccine Corbevax and select to an optimum formulation. Healthy adults (n=460) without COVID-19 vaccination or SARS-CoV-2 infection in the Phase-1/2 study were randomly divided into four vaccine formulation groups. A low incidence of adverse events was reported post-vaccination. All formulations showed similar profiles of humoral and cellular immune responses that were associated with the content of CpG1018 adjuvant in the vaccine. In the Phase-2 study, 750 µg of CpG1018 showed significant improvement (> 4-fold increase from baseline) in immune responses, including the titres of anti-RBD IgG and neutralising antibody (nAb), and cellular immune responses, while maintaining the safety profile. Antibodies persisted consistently for 12 months after the second dose of vaccine. Corbevax (two-dose schedule with 28 days of interval between doses) was well tolerated with no observed safety concerns. Previous observations from efficacy studies by Moderna and AstraZeneca and the correlation between nAb titres post-vaccination and a human convalescent serum panel showed that Corbevax induced significantly high nAb titres. These studies were prospectively registered with the Clinical Trial Registry of India (CTRI/2021/06/034014 and CTRI/2020/11/029032). Bill & Melinda Gates Foundation, BIRAC-Division of Department of Biotechnology, Govt of India, and the Coalition for Epidemic Preparedness Innovations funded this study.
Sections du résumé
BACKGROUND
BACKGROUND
We assessed the efficacy of a receptor-binding domain (RBD)-based protein subunit COVID-19 vaccine.
METHODS
METHODS
A randomised Phase-1/2 trial followed by a Phase-2 trial were conducted to assess the safety and immunogenicity of the COVID-19 vaccine Corbevax and select to an optimum formulation. Healthy adults (n=460) without COVID-19 vaccination or SARS-CoV-2 infection in the Phase-1/2 study were randomly divided into four vaccine formulation groups.
FINDINGS
RESULTS
A low incidence of adverse events was reported post-vaccination. All formulations showed similar profiles of humoral and cellular immune responses that were associated with the content of CpG1018 adjuvant in the vaccine. In the Phase-2 study, 750 µg of CpG1018 showed significant improvement (> 4-fold increase from baseline) in immune responses, including the titres of anti-RBD IgG and neutralising antibody (nAb), and cellular immune responses, while maintaining the safety profile. Antibodies persisted consistently for 12 months after the second dose of vaccine.
INTERPRETATIONS
CONCLUSIONS
Corbevax (two-dose schedule with 28 days of interval between doses) was well tolerated with no observed safety concerns. Previous observations from efficacy studies by Moderna and AstraZeneca and the correlation between nAb titres post-vaccination and a human convalescent serum panel showed that Corbevax induced significantly high nAb titres. These studies were prospectively registered with the Clinical Trial Registry of India (CTRI/2021/06/034014 and CTRI/2020/11/029032).
FUNDING
BACKGROUND
Bill & Melinda Gates Foundation, BIRAC-Division of Department of Biotechnology, Govt of India, and the Coalition for Epidemic Preparedness Innovations funded this study.
Identifiants
pubmed: 35970020
pii: S2352-3964(22)00399-1
doi: 10.1016/j.ebiom.2022.104217
pmc: PMC9372721
pii:
doi:
Substances chimiques
Antibodies, Neutralizing
0
Antibodies, Viral
0
COVID-19 Vaccines
0
Immunoglobulin G
0
Protein Subunits
0
Types de publication
Clinical Trial, Phase I
Clinical Trial, Phase II
Journal Article
Multicenter Study
Randomized Controlled Trial
Langues
eng
Sous-ensembles de citation
IM
Pagination
104217Informations de copyright
Copyright © 2022 The Author(s). Published by Elsevier B.V. All rights reserved.
Déclaration de conflit d'intérêts
Declaration of interests ST, VP, KT, SG, VY, RM, MK, and SKM are employees of Biological E Limited, and do not have any stock options or incentives. All the other participating authors declare no conflicts of interest.