Safety and Immunogenicity of SARS-CoV-2 Recombinant Spike Protein Vaccine in Children and Adolescents in India
Authors: Gunale Bhagwat , Kapse Dhananjay , Kar Sonali , Bavdekar Ashish , Kohli Sunil , Lalwani Sanjay , Meshram Sushant , Raut Abhishek , Kulkarni Praveen , Samuel Clarence , Munshi Renuka , Gupta Madhu , Plested Joyce S. , Cloney-Clark Shane , Zhu MingZhu , Pryor Melinda , Hamilton Stephanie , Thakar Madhuri , Shete Ashwini , Dharmadhikari Abhijeet , Bhamare Chetanraj , Shaligram Umesh , Poonawalla Cyrus S. , Mallory Raburn M. , Glenn Gregory M. , Kulkarni Prasad S. ,   COVOVAX-Ped study group, Samantaray Pramod C , Kawade Anand , Gondhali Arunkumar , Jain Vineet , Goyal Nidhi , Arya Alok , Rongsen-Chandola Temsunaro , Palkar Sonali , Hanumante Neeta M , Bhatnagar Manoj H , Shyamkuwar Chetna A , Garg B S , Meshram Payal , Deotale Vijayshri , Mahajan Kamlesh , Kalantri Ashwini , V Prajwala H , Rao Vijayalakshmi V , Kamra Deepshikha , Singh Aradhana , Kumbhar Dipti , Shafiq Nusrat , Sharma Indrakshi , Choche Rahul , Ghatage Deepak , Salvi Sugam 
Published: July 2023

ImportanceThe recombinant COVID-19 vaccine NVX-CoV2373 has demonstrated efficacy of approximately 90% in adults; however, its safety and efficacy in children is unknown.ObjectiveTo 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 ParticipantsThis 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.InterventionsTwo doses of 0.5-mL SII-NVX-CoV2373 or placebo were administered intramuscularly on days 1 and 22.Main Outcomes and MeasuresPrimary 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.ResultsA 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 RelevanceSII-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 RegistrationClinical Trials Registry of India Identifier: CTRI/2021/02/031554