Assessing the safety of inactivated SARS-CoV-2 vaccine (CoronaVac) in healthy children and adolescents

By Marzia KhanJun 30 2021

Clinical trials for vaccines and therapies against the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) have predominantly focused on adults thus far. With a few rare exceptions, healthy children and adolescents infected with the virus often present with either asymptomatic or mild manifestations of coronavirus disease 2019 (COVID-19).

However, due to the transmission risk that children and adolescents pose as carriers of the virus, vaccinations for this group may also be important in managing its spread to more vulnerable individuals. Moreover, many children and adolescents who may have underlying conditions or co-morbidities can be severely affected by SARS-CoV-2 once infected, and new research suggests that a severe complication from the virus can cause multisystem inflammatory syndrome in this group. This can result in children suffering from myocardial dysfunction, shock as well as respiratory failure, which may require intensive care.

These risk factors illustrate the significance of testing the efficacy of vaccines for this group of individuals.

New clinical trial data, recently published in The Lancet’s Infectious Diseases, presents an initial report on the effect of an inactivated SARS-CoV-2 vaccine, CoronaVac, on children and adolescents from ages 3-17 in a double-blind, randomized setting.

Study: 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. Image Credit: LookerStudio / Shutterstock

The researchers from China had previously assessed this vaccine, which utilizes an inactivated form of the virus, developed by Sinovac Life Sciences, for those aged 18-59 and those over 60, finding it safe and well-tolerated in this group.

Inactivated viruses

Purified and inactivated viruses have traditionally been used in medicine for the development of vaccines. The CoronaVac vaccine, which utilizes inactivated viruses, had been found to provide partial or complete protection in macaque monkeys when investigating its effect on SARS-CoV-2 infections. The vaccine was able to provide a semblance of protection without antibody-dependent enhancement of the infection.

The vaccine preparation procedure consisted of the SARS-CoV-2 virus being propagated in African green monkey kidney cells. Post incubation, the virus was harvested and then inactivated with β-propiolactone, then concentrated and purified before being adsorbed into aluminum hydroxide.  The complex was then diluted in sodium chloride, phosphate-buffered saline as well as water; it was then sterilized and filtered for injection use.

CoronaVac trials

The first and second (of three) phases for CoronaVac’s clinical trials in children and adolescents were launched in October 2020. These have aimed to test the safety, immunogenicity and tolerability of the vaccine in this group.

Due to differences in the weight of children and adolescents compared to adults, the researchers employed different dosages in these trials, such as 1.5 μg and 3.0 μg.

The trials used 72 participants for the phase 1 trial consisting of different age groups (3–5 years, 6–11 years, and 12–17 years). These participants were either given the block 1, a low dose of 1.5 μg or block 2, a higher dose of 3.0 μg. The participants were randomly assigned either the vaccine or a control placebo of aluminum hydroxide adjuvant only.

After 7 days of follow-up at the end of the phase 1 stage, phase 2 was then initiated. The safety criteria which the participants were required to pass included having no life-threatening adverse side effects, as well as there being no more than 15% of severe adverse reactions due to the vaccine, and no other safety concerns from the data monitoring committee. After these safety concerns were met, the phase 2 trial was initiated, with 480 participants being recruited.

Findings

The researchers found that two doses of CoronaVac seemed to be safe and well-tolerated at 1.5 μg and 3.0 μg doses in children and adolescents aged 3-17 years. The side effects and reactions from the vaccine were mild to moderate in severity and were short-lasting. The most commonly reported symptom was injection-site pain, which was more prevalent in the 12-17 age group. This may have been the reason behind the high prevalence of adverse reactions in this group compared to the younger age groups included in the study. The study mentions the results were similar to the results from their previous study in adults and the elderly.

The seroconversion rates of neutralizing antibodies in children and adolescents with both doses were at approximately 96% after two doses of the vaccine. Additionally, when investigating the neutralizing antibody responses in different age groups, an exploratory analysis illustrated a lack of significant differences.

The team’s trial data has provided preliminary insight into how safe and tolerable the CoronaVac inactivated vaccine may be in children and adolescents (aged 3-17). However, due to the small sample size in these trials, the results cannot be seen as being representative of the population at large.

The present data also lacks an assessment of T cell responses in this group, which would have been beneficial to include when investigating inactivated vaccines.

Further research – including a third and final phase of clinical trials with a larger sample size – will be needed to validate these promising findings.