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

Adult Humans Child Adolescent Child, Preschool SARS-CoV-2 Prospective Studies COVID-19 / prevention & control Vaccines Double-Blind Method Immunoglobulin G Immunogenicity, Vaccine Antibodies, Viral Antibodies, Neutralizing

Adverse events Covid-19 Neutralizing antibodies Protein subunit Receptor binding domain SARS-CoV-2 Vaccine

Journal

Vaccine

ISSN: 1873-2518

Titre abrégé: Vaccine

Pays: Netherlands

ID NLM: 8406899

Informations de publication

Date de publication:
22 11 2022

Historique:

received: 16 06 2022

revised: 10 10 2022

accepted: 14 10 2022

pubmed: 4 11 2022

medline: 22 11 2022

entrez: 3 11 2022

Statut: ppublish

Résumé

After establishing safety and immunogenicity of Biological-E's CORBEVAX™ vaccine in adult population (18-80 years) in Phase 1-3 studies, vaccine is further tested in children and adolescents in this study. This is a phase-2/3 prospective, randomised, double-blind, placebo-controlled study evaluating safety, reactogenicity, tolerability and immunogenicity of CORBEVAX™ vaccine in children and adolescents 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 CORBEVAX™ vaccine or Placebo in 3:1 ratio. The safety profile of CORBEVAX™ 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, CORBEVAX™ 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 CORBEVAX™ vaccinated subjects with minimal effect on IL-4 cytokine secretion. The safety profile of CORBEVAX™ 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 CORBEVAX™ vaccine is highly immunogenic 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.

Sections du résumé

BACKGROUND

METHODS

This is a phase-2/3 prospective, randomised, double-blind, placebo-controlled study evaluating safety, reactogenicity, tolerability and immunogenicity of CORBEVAX™ vaccine in children and adolescents 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 CORBEVAX™ vaccine or Placebo in 3:1 ratio.

FINDINGS

The safety profile of CORBEVAX™ 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, CORBEVAX™ 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 CORBEVAX™ vaccinated subjects with minimal effect on IL-4 cytokine secretion.

INTERPRETATIONS

The safety profile of CORBEVAX™ 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 CORBEVAX™ vaccine is highly immunogenic 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.

Identifiants

DOI: 10.1016/j.vaccine.2022.10.045 PMID: 36328879

pubmed: 36328879

pii: S0264-410X(22)01308-1

doi: 10.1016/j.vaccine.2022.10.045

pii:

doi:

Substances chimiques

Vaccines 0

Immunoglobulin G 0

Antibodies, Viral 0

Antibodies, Neutralizing 0

Banques de données

CTRI

['TRI/2021/10/037066']

Types de publication

Randomized Controlled Trial Clinical Trial, Phase II Clinical Trial, Phase III Journal Article Research Support, Non-U.S. Gov't

Langues

eng

Sous-ensembles de citation

Pagination

7130-7140

Informations de copyright

Déclaration de conflit d'intérêts

Declaration of Competing Interest The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: ST, VP, SG, VY, RM, PVS, KT, MK, SKM, SA and ASJ are employees of Biological E Limited and they don’t have any incentives or stock options. All other participating authors declare no competing interests.