Safety, tolerability and immunogenicity of Biological E?s CORBEVAXTM vaccine in children and adolescents: A prospective, randomised, double-blind, placebo controlled, phase-2/3 study

Background: After establishing safety and immunogenicity of Biological-E's CORBEVAXTM vaccine in adult population (18-80 years) in Phase 1-3 studies, vaccine is further tested in children and adolescents in this study.Methods: This is a phase-2/3 prospective, randomised, double-blind, placebo-controlled study evaluating safety, reactogenicity, tolerability and immunogenicity of CORBEVAXTM vaccine in children and adoles-cents of either gender between <18 to >= 12 years of age in Phase-2 and <18 to >= 5 years of age in Phase-Phase-2/Phase-3 with placebo as a control. This study has two age sub-groups; subgroup-1 with subjects <18 to >= 12 years of age and subgroup-2 with subjects <12 to >= 5 years of age. In both sub groups, eligible subjects (SARS-CoV-2 RT-PCR negative and seronegative at baseline) were randomized to receive either CORBEVAXTMvaccine or Placebo in 3:1 ratio.Findings: The safety profile of CORBEVAXTM vaccine in both pediatric cohorts was comparable to the placebo-control group. Majority of reported adverse events (AEs) were mild in nature. No severe or serious-AEs, medically attended AEs (MAAEs) or AEs of special interest (AESI) were reported during the study period and all reported AEs resolved without any sequelae. In both pediatric age groups, CORBEVAXTM vaccinated subjects showed significant improvement in humoral immune-responses in terms of anti-RBD-IgG concentrations, anti-RBD-IgG1 titers, neutralizing-antibody (nAb)-titers against Ancestral-Wuhan and Delta-strains. Significantly high interferon-gamma immune-response (cellular) was elicited by CORBEVAXTM vaccinated subjects with minimal effect on IL-4 cytokine secretion.Interpretations: The safety profile of CORBEVAXTM vaccine in <18 to >= 5 years' children and adolescents was found to be safe and tolerable. Significant increase in anti-RBD-IgG and nAb-titers and IFN-gamma immune-responses were observed post-vaccination in both pediatric age sub-groups. The nAb titers observed in both the pediatric age cohorts were non-inferior to the adult cohort (BECT069 study) in terms of ratio of the GMT's of both the cohorts. This study shows that CORBEVAXTM vaccine is highly immuno-genic and can be safely administered to pediatric population as young as 5 years old. The study was prospectively registered with clinical trial registry of India-CTRI/2021/10/037066.(c) 2022 Elsevier Ltd. All rights reserved.