PMID- 36328879
OWN - NLM
STAT- MEDLINE
DCOM- 20221121
LR  - 20230126
IS  - 1873-2518 (Electronic)
IS  - 0264-410X (Linking)
VI  - 40
IP  - 49
DP  - 2022 Nov 22
TI  - 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.
PG  - 7130-7140
LID - S0264-410X(22)01308-1 [pii]
LID - 10.1016/j.vaccine.2022.10.045 [doi]
AB  - BACKGROUND: 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. 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.
CI  - Copyright (c) 2022 Elsevier Ltd. All rights reserved.
FAU - Thuluva, Subhash
AU  - Thuluva S
AD  - Biological E Limited, 18/1&3, Azamabad, Hyderabad 500 020, Telangana, India. 
      Electronic address: subhash.thuluva@biologicale.com.
FAU - Paradkar, Vikram
AU  - Paradkar V
AD  - Biological E Limited, 18/1&3, Azamabad, Hyderabad 500 020, Telangana, India.
FAU - Gunneri, SubbaReddy
AU  - Gunneri S
AD  - Biological E Limited, 18/1&3, Azamabad, Hyderabad 500 020, Telangana, India.
FAU - Yerroju, Vijay
AU  - Yerroju V
AD  - Biological E Limited, 18/1&3, Azamabad, Hyderabad 500 020, Telangana, India.
FAU - Mogulla, Rammohan Reddy
AU  - Mogulla RR
AD  - Biological E Limited, 18/1&3, Azamabad, Hyderabad 500 020, Telangana, India.
FAU - Suneetha, Pothakamuri Venkata
AU  - Suneetha PV
AD  - Biological E Limited, 18/1&3, Azamabad, Hyderabad 500 020, Telangana, India.
FAU - Turaga, Kishore
AU  - Turaga K
AD  - Biological E Limited, 18/1&3, Azamabad, Hyderabad 500 020, Telangana, India.
FAU - Kyasani, Mahesh
AU  - Kyasani M
AD  - Biological E Limited, 18/1&3, Azamabad, Hyderabad 500 020, Telangana, India.
FAU - Manoharan, Senthil Kumar
AU  - Manoharan SK
AD  - Biological E Limited, 18/1&3, Azamabad, Hyderabad 500 020, Telangana, India.
FAU - Adabala, Srikanth
AU  - Adabala S
AD  - Biological E Limited, 18/1&3, Azamabad, Hyderabad 500 020, Telangana, India.
FAU - Sri Javvadi, Aditya
AU  - Sri Javvadi A
AD  - Biological E Limited, 18/1&3, Azamabad, Hyderabad 500 020, Telangana, India.
FAU - Medigeshi, Guruprasad
AU  - Medigeshi G
AD  - Bioassay Laboratory, Translational Health Science and Technology Institute, 
      Faridabad 121001, India.
FAU - Singh, Janmejay
AU  - Singh J
AD  - Bioassay Laboratory, Translational Health Science and Technology Institute, 
      Faridabad 121001, India.
FAU - Shaman, Heena
AU  - Shaman H
AD  - Bioassay Laboratory, Translational Health Science and Technology Institute, 
      Faridabad 121001, India.
FAU - Binayke, Akshay
AU  - Binayke A
AD  - Bioassay Laboratory, Translational Health Science and Technology Institute, 
      Faridabad 121001, India.
FAU - Zaheer, Aymaan
AU  - Zaheer A
AD  - Bioassay Laboratory, Translational Health Science and Technology Institute, 
      Faridabad 121001, India.
FAU - Awasthi, Amit
AU  - Awasthi A
AD  - Bioassay Laboratory, Translational Health Science and Technology Institute, 
      Faridabad 121001, India.
FAU - Narang, Manish
AU  - Narang M
AD  - Guru Teg Bahadur Hospital (GTB), Delhi, India.
FAU - Nanjappa, Pradeep
AU  - Nanjappa P
AD  - Cheluvamba Hospital, Mysore, Karnataka, India.
FAU - Mahantshetti, Niranjana
AU  - Mahantshetti N
AD  - KLES Dr. Prabhakar Kore Hospital & Medical Research Centre, Belagavi, Karnataka, 
      India.
FAU - Swarup Garg, Bishan
AU  - Swarup Garg B
AD  - Mahatma Gandhi Institute of Medical Sciences (MGIMS), Wardha, Maharashtra, India.
FAU - Pandey, Anil Kumar
AU  - Pandey AK
AD  - ESIC Medical College & Hospital, Faridabad, Haryana, India.
LA  - eng
SI  - CTRI/TRI/2021/10/037066
PT  - Clinical Trial, Phase II
PT  - Clinical Trial, Phase III
PT  - Journal Article
PT  - Randomized Controlled Trial
PT  - Research Support, Non-U.S. Gov't
DEP - 20221031
PL  - Netherlands
TA  - Vaccine
JT  - Vaccine
JID - 8406899
RN  - 0 (Vaccines)
RN  - 0 (Immunoglobulin G)
RN  - 0 (Antibodies, Viral)
RN  - 0 (Antibodies, Neutralizing)
SB  - IM
MH  - Adult
MH  - Humans
MH  - Child
MH  - Adolescent
MH  - Child, Preschool
MH  - SARS-CoV-2
MH  - Prospective Studies
MH  - *COVID-19/prevention & control
MH  - *Vaccines
MH  - Double-Blind Method
MH  - Immunoglobulin G
MH  - Immunogenicity, Vaccine
MH  - Antibodies, Viral
MH  - Antibodies, Neutralizing
OTO - NOTNLM
OT  - Adverse events
OT  - Covid-19
OT  - Neutralizing antibodies
OT  - Protein subunit
OT  - Receptor binding domain
OT  - SARS-CoV-2
OT  - Vaccine
COIS- 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.
EDAT- 2022/11/04 06:00
MHDA- 2022/11/22 06:00
CRDT- 2022/11/03 23:05
PHST- 2022/06/16 00:00 [received]
PHST- 2022/10/10 00:00 [revised]
PHST- 2022/10/14 00:00 [accepted]
PHST- 2022/11/04 06:00 [pubmed]
PHST- 2022/11/22 06:00 [medline]
PHST- 2022/11/03 23:05 [entrez]
AID - S0264-410X(22)01308-1 [pii]
AID - 10.1016/j.vaccine.2022.10.045 [doi]
PST - ppublish
SO  - Vaccine. 2022 Nov 22;40(49):7130-7140. doi: 10.1016/j.vaccine.2022.10.045. Epub 
      2022 Oct 31.