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. 2023 Jul 31;177(9):911-920.
doi: 10.1001/jamapediatrics.2023.2552. Online ahead of print.

Safety and Immunogenicity of SARS-CoV-2 Recombinant Spike Protein Vaccine in Children and Adolescents in India: A Phase 2-3 Randomized Clinical Trial

Bhagwat Gunale  1 , Dhananjay Kapse  1 , Sonali Kar  2 , Ashish Bavdekar  3 , Sunil Kohli  4 , Sanjay Lalwani  5 , Sushant Meshram  6 , Abhishek Raut  7 , Praveen Kulkarni  8 , Clarence Samuel  9 , Renuka Munshi  10 , Madhu Gupta  11 , Joyce S Plested  12 , Shane Cloney-Clark  12 , MingZhu Zhu  12 , Melinda Pryor  13 , Stephanie Hamilton  13 , Madhuri Thakar  14 , Ashwini Shete  14 , Abhijeet Dharmadhikari  1 , Chetanraj Bhamare  1 , Umesh Shaligram  1 , Cyrus S Poonawalla  1 , Raburn M Mallory  12 , Gregory M Glenn  12 , Prasad S Kulkarni  1 ; COVOVAX-Ped study group
Collaborators, Affiliations

Safety and Immunogenicity of SARS-CoV-2 Recombinant Spike Protein Vaccine in Children and Adolescents in India: A Phase 2-3 Randomized Clinical Trial

Bhagwat Gunale et al. JAMA Pediatr. .

Abstract

Importance: The recombinant COVID-19 vaccine NVX-CoV2373 has demonstrated efficacy of approximately 90% in adults; however, its safety and efficacy in children is unknown.

Objective: To assess the noninferiority of SII-NVX-CoV2373 in children and adolescents compared to adults and to evaluate its safety in comparison with placebo.

Design, setting, and participants: This phase 2-3 observer-blind randomized clinical trial was conducted in 2 cohorts, children (aged 2 to 11 years) and adolescents (aged 12 to 17 years) between August 2021 and August 2022. Participants were randomized 3:1 to SII-NVX-CoV2373 or placebo and monitored for 179 days. The participants, study team, and laboratory staff were blinded. This was a multicenter study conducted across 10 tertiary care hospitals in India. Exclusion criteria included previous COVID-19 infection or vaccination, immunocompromised condition, and immunosuppressive medications.

Interventions: Two doses of 0.5-mL SII-NVX-CoV2373 or placebo were administered intramuscularly on days 1 and 22.

Main outcomes and measures: Primary outcomes were geometric mean titer ratio of both anti-spike (anti-S) IgG and neutralizing antibodies (NAbs) between both pediatric age groups to that of adults on day 36. Noninferiority was concluded if the lower bound of 95% CI of this ratio was greater than 0.67 for each age group. Both the antibodies were assessed for the index strain and for selected variants at various time points. Solicited adverse events (AEs) were recorded for 7 days after each vaccination, unsolicited AEs were recorded for 35 days, and serious AEs and AEs of special interest were recorded for 179 days.

Results: A total of 460 children in each age cohort were randomized to receive vaccine or placebo. The mean (SD) age was 6.7 (2.7) years in the child cohort and 14.3 (1.6) years in the adolescent cohort; 231 participants (50.2%) in the child cohort and 218 in the adolescent cohort (47.4%) were female. Both anti-S IgG and NAb titers were markedly higher in the SII-NVX-CoV2373 group than in the placebo group on both day 36 and day 180. The geometric mean titer ratios compared to those in adults were 1.20 (95% CI, 1.08-1.34) and 1.52 (95% CI, 1.38-1.67) for anti-S IgG in adolescents and children, respectively; while for NAbs, they were 1.33 (95% CI, 1.17-1.50) and 1.93 (95% CI, 1.70-2.18) in adolescents and children, respectively, indicating noninferiority. SII-NVX-CoV2373 also showed immune responses against variants studied. Injection site reactions, fever, headache, malaise, and fatigue were common solicited AEs. There were no AEs of special interest and no causally related serious AEs.

Conclusions and relevance: SII-NVX-CoV2373 was safe and well tolerated in children and adolescents in this study. The vaccine was highly immunogenic and may be used in pediatric vaccination against COVID-19.

Trial registration: Clinical Trials Registry of India Identifier: CTRI/2021/02/031554.

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Conflict of interest statement

Conflict of Interest Disclosures: Drs Gunale, Kapse, Bhamare, Shaligram, P. S. Kulkarni, and Mr Dharmadhikari are employed by Serum Institute of India, which funded the present study and manufacture the study vaccine, during the conduct of the study and outside the submitted work. Drs Plested and Zhu and Ms Cloney-Clark reported employment and stock holdings at Novavax during the conduct of the study. Dr Pryor reported a contract between Serum Institute of India and 360biolabs during the conduct of the study. Dr Hamilton reported payment from Serum Institute of India through a contract with 360biolabs to complete testing during the conduct of the study; additionally, 360biolabs received financial compensation from Novavax for contracted work outside the submitted work. Dr Poonawalla is chairman and managing director of Serum Institute of India, which funded this study and manufactured the study vaccine, during the conduct of the study and outside the submitted work. Dr Mallory reports employment and stock holdings at Novavax during the conduct of the study. Dr Glenn reported personal fees from Novavax during the conduct of the study and outside the submitted work; in addition, Dr Glenn had a patent pending for Novavax and is employed by Novavax. No other disclosures were reported.

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