Discussion
confusion, infections
ADVERSE REACTIONS, INFECTIONS
In this phase IV, randomized, double-blind clinical trial in healthy children and adolescents aged 3-17 years, we found equivalent immune responses after CoronaVac vaccination among all comparative groups of different lots or workshops, where the 95%CIs of GMT ratios were all within the equivalence criterion of [0.67, 1.5]. These results were consistent with our previous phase IV study in healthy adults aged 26-45 years, where lot-to-lot consistency was also observed for three lots of CoronaVac on a commercial scale, with GMT ratios of 1.16 (95%CI: 1.01, 1.32), 1.15 (95%CI: 1.01, 1.32), and 0.99 (95%CI: 0.87, 1.14) for each pair of lots, respectively (In this trial, the observed GMT of neutralizing antibody was 126.42 for all participants at 28 days after full course of vaccination, ranging from 118.78 to 134.97 among seven lots; and the immunogenicity level in children and adolescents were much higher than that in adults aged 26-45 years in our previous lot-to-lot consistency study, of which the observed GMT were 68.4 ranging from 65.0 to 75.2 among three lots (In addition, the incidences of adverse reactions were similar among seven lots in this trial, with no statistical difference. CoronaVac showed a well-tolerated safety profile in children and adolescents that most adverse reactions were mild (grade 1) in severity, with no SAE and AESI reported. These findings were consistent with our previous phase I/II study as well as the following homologous booster study in children and adolescents (There were several limitations in this study. Firstly, given that when the study started, large vaccination campaigns had been implemented and good safety profiles had been observed for CoronaVac in real world settings, the study period was only set up to 28 days after two-dose vaccination. The relatively short follow-up period could not evaluate a long-term immunogenicity and safety of CoronaVac among children and adolescents. Secondly, only neutralizing antibody titers against ancestral strain was tested for the immunogenicity assessment. Due to continuous genetic mutations of SARS-CoV-2 and changes in its characteristics, we need to assess the lot-to-lot consistency of CoronaVac against SARS-CoV-2 variants. Thirdly, this study was conducted during the period of China’s dynamic Zero-COVID policy implementation, and very few COVID-19 cases occurred. This study background is different form the read word settings in other countries, but it can also avoid the confusion causing by SARS-CoV-2 natural infections.In conclusion, among healthy children and adolescents aged 3-17 years, two doses of CoronaVac are well-tolerated and can induce a good and similar immune response among seven lots from three workshops. Lot-to-lot consistency evidence indicates stable manufacturing of commercial-scale CoronaVac by Sinovac.