CoronaVac (an inactivated vaccine against SARS-CoV-2) was previously shown to be effective and safe in adults. This is the first Phase 1/2 trial evaluating the tolerance and immunogenicity of a SARS-CoV-2 vaccine in adolescents and young children.
Determining the safety of a therapy, whether vaccination or otherwise, in a low-risk group such as this has to weigh the risks of rare adverse events associated with vaccination against the benefits, which are likely small in this patient population. .
Study questions:
What is the safety, tolerability and immunogenicity of the CoronaVac vaccine against coronavirus disease 2019 (COVID-19) in children and adolescents aged 3 to 17 years?
Methods:
CoronaVac is an inactivated vaccine for acute respiratory syndrome coronavirus 2 (SARS-CoV-2) developed by Sinovac Life Sciences (Beijing, China) that has been shown to be effective and safe in adults.
This study was a phase 1/2 , double-blind, randomized, controlled clinical trial of CoronaVac in healthy children and adolescents aged 3 to 17 years at the Hebei Provincial Center for Disease Control and Prevention in Zanhuang, Hebei, China.
Intramuscular injections of the vaccine or aluminum hydroxide were only administered in 2 doses (day 0 and day 28).
The study consisted of two phases: a phase 1 trial in 72 participants with a decrease in age and an increase in dose: participants in each age group (3-5 years, 6-11 years and 12-17 years ) were recruited in order from the low-dose stage (1.5 μg) to the high-dose stage (3.0 μg).
In the second phase, participants (n = 480) with safety data for 7-day follow-up were randomized (2:2:1) to receive CoronaVac at 1.5 μg or 3.0 μg per dose, or just alum. The primary safety endpoint was adverse reactions within 28 days of each injection in all participants who received ≥1 dose.
The primary endpoint of immunogenicity was the seroconversion rate of neutralizing antibody to live SARS-CoV-2 at 28 days after the second injection.
Results:
A total of 550 participants received ≥1 dose of vaccine or alum only (n = 71 for phase 1 and n = 479 for phase 2; safety population).
In the combined phase 1 and phase 2 safety profile, any adverse reaction within 28 days of injection occurred in 56 (26%) of 219 participants in the 1.5 μg group, 63 (29% ) of 217 in the 3.0 μg group, and 27 (24%) of 114 in the alum-only group, with no 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 1.5 μg group, 35 (16 %) of 217 in the 3.0 μg group, and two (2%) in the alum-only group.
The prevalence of adverse reactions was highest in participants aged 12 to 17 years (35%), followed by those aged 3 to 5 years (26%) and 6 to 11 years (18%) of 204 participants.
In phase 1, neutralizing antibody seroconversion was observed after the second dose in all participants in both the 1.5 μg group and the 3.0 μg group.
In phase 2, seroconversion was observed in 180 of 186 participants (96.8% [93.1-98.8]) in the 1.5 μg group and all participants in the 3.0 μg group.
Antibody titers were slightly higher in the 3.0 μg group.
There were no significant differences in seroconversion rates between age subgroups.
Conclusions:
CoronaVac was well tolerated and induced humoral responses in children and adolescents aged 3 to 17 years.
Interpretation
CoronaVac was well tolerated and safe and induced humoral responses in children and adolescents aged 3 to 17 years. The neutralizing antibody titers induced by the 30 µg dose were higher than those by the 1.5 µg dose. The results support the use of a dose of 3·0 μg with a two-immunization schedule for further studies in children and adolescents.
Perspective: This first phase 1/2 clinical trial evaluating the safety of a SARS-CoV-2 vaccine in children and adolescents as young as 3 years suggests that the vaccine is well tolerated and immunogenic. While the primary safety endpoint of the trial was met; Determining the safety of a therapy, whether vaccination or other, in such a low-risk group has to weigh the risks of rare adverse events associated with vaccination against the benefits; which are possibly small in this population, in which COVID-19 is a predominantly asymptomatic to mild syndrome. Rare events, such as myocarditis associated with other COVID-19 vaccines, cannot be studied in these small trials and are usually identified in post-marketing surveillance. Ensuring that the benefits of COVID-19 vaccination outweigh the risks will require much more study to establish. |
