Safety, tolerability, and immunogenicity of an inactivated SARS-CoV-2 vaccine (CoronaVac) in healthy children and adolescents: a double-blind, randomised, controlled, phase 1/2 clinical trial
Authors: B Han, Y Song, C Li, W Yang, Q Ma, Z Jiang, M Li, X Lian, W Jiao, L Wang, Q Shu, Z Wu, Y Zhao, Q Li, Q Gao
Published in: The Lancet
Background A vaccine against SARS-CoV-2 for children and adolescents will play an important role in curbing the COVID-19 pandemic. Here we aimed to assess the safety, tolerability, and immunogenicity of a candidate COVID-19 vaccine, CoronaVac, containing inactivated SARS-CoV-2, in children and adolescents aged 3–17 years.
Methods We did a double-blind, randomised, controlled, phase 1/2 clinical trial of CoronaVac in healthy children and adolescents aged 3–17 years old at Hebei Provincial Center for Disease Control and Prevention in Zanhuang (Hebei, China). Individuals with SARS-CoV-2 exposure or infection history were excluded. Vaccine (in 0·5 mL aluminum hydroxide adjuvant) or aluminum hydroxide only (alum only, control) was given by intramuscular injection in two doses (day 0 and day 28). We did a phase 1 trial in 72 participants with an age de-escalation in three groups and dose-escalation in two blocks (1·5μg or 3·0μg per injection). Within each block, participants were randomly assigned (3:1) by means of block randomisation to receive CoronaVac or alum only. In phase 2, participants were randomly assigned (2:2:1) by means of block randomisation to receive either CoronaVac at 1·5μg or 3·0μg per dose, or alum only. All participants, investigators, and laboratory staff were masked to group allocation. The primary safety endpoint was adverse reactions within 28 days after each injection in all participants who received at least one dose. The primary immunogenicity endpoint assessed in the per-protocol population was seroconversion rate of neutralising antibody to live SARS-CoV-2 at 28 days after the second injection. This study is ongoing and is registered with ClinicalTrials.gov, NCT04551547.
Findings Between Oct 31, 2020, and Dec 2, 2020, 72 participants were enrolled in phase 1, and between Dec 12, 2020, and Dec 30, 2020, 480 participants were enrolled in phase 2. 550 participants received at least one dose of vaccine or alum only (n=71 for phase 1 and n=479 for phase 2; safety population). In the combined safety profile of phase 1 and phase 2, any adverse reactions within 28 days after injection occurred in 56 (26%) of 219 participants in the 1·5μg group, 63 (29%) of 217 in the 3·0μg group, and 27 (24%) of 114 in the alum-only group, without significant difference (p=0·55). Most adverse reactions were mild and moderate in severity. Injection site pain was the most frequently reported event (73 [13%] of 550 participants), occurring in 36 (16%) of 219 participants in the 1·5μg group, 35 (16%) of 217 in the 3·0μg group, and two (2%) in the alum-only group. As of June 12, 2021, only one serious adverse event of pneumonia has been reported in the alum-only group, which was considered unrelated to vaccination. In phase 1, seroconversion of neutralising antibody after the second dose was observed in 27 of 27 participants (100·0% [95% CI 87·2–100·0]) in the 1·5μg group and 26 of 26 participants (100·0% [86·8-100·0]) in the 3·0μg group, with the geometric mean titres of 55·0 (95% CI 38·9–77·9) and 117·4 (87·8–157·0). In phase 2, seroconversion was seen in 180 of 186 participants (96·8% [93·1–98·8]) in the 1·5μg group and 180 of 180 participants (100·0% [98·0–100·0]) in the 3·0μg group, with the geometric mean titres of 86·4 (73·9–101·0) and 142·2 (124·7–162·1). There were no detectable antibody responses in the alum-only groups.
Interpretation CoronaVac was well tolerated and safe and induced humoral responses in children and adolescents aged 3–17 years. Neutralising antibody titres induced by the 3·0μg dose were higher than those of the 1·5μg dose. The results support the use of 3·0μg dose with a two-immunisation schedule for further studies in children and adolescents.