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Safety, tolerability, and immunogenicity of an inactivated SARS-CoV-2 vaccine (CoronaVac) in healthy adults aged 60 years and older: a randomised, double-blind, placebo-controlled, phase 1/2 clinical trial

Our take —

CoronaVac (developed by Sinovac) was demonstrated in the phase 1/2 trial in Heibei, China, to be safe in older adults ages 60 years and older, and was successfully able to induce neutralizing antibody responses. A 3ug two-dose immunization schedule will move forward into phase 3 trials because it is similarly effective to the 6ug dose and more effective than the 1.5ug dose in inducing production of neutralizing antibodies.

Study design

Randomized Controlled Trial

Study population and setting

This study includes results of a phase 1/2 clinical trial testing the safety, tolerability, and immunogenicity of the CoronaVac vaccine (developed by Sinovac), which contains whole inactivated SARS-CoV-2, in adults age 60 years and older in Hebei, China. Phase 1 included 72 participants testing 3ug and 6ug doses, as well as placebo, in a two-dose schedule administered on days 0 and 28. In phase 2, there were 350 participants receiving either 1.5ug, 3ug, 6ug, or placebo also in the same two-dose regimen. The trial studied adverse reactions and seroconversion to production of neutralizing antibodies within 28 days after each injection.

Summary of Main Findings

Mild to moderate adverse reactions occurred in about 20% of participants regardless of dose, with the most common reactions being injection site pain (9%) and fever (3%). No vaccine-related serious-adverse events have been reported. Phase 1 data showed that seroconversion rates after only one dose of CoronaVac were low, underscoring the need for a two-dose regimen. In phase 2, seroconversion was seen in 90% participants in the 1.5ug group, 98% of the 3ug group, and 99% of the 6ug group. Seroconversion rates by 28 days after the second dose were higher than 94% in both 3ug and 6ug groups for all participant age groups studied (60-64, 65-69, and 70+ years old).

Study Strengths

This trial tested multiple doses to determine the smallest dose possible with the greatest immunogenicity, and studied the effects of a two-dose immunization schedule. It also tested the CoronaVac vaccine in older individuals, who are among the most susceptible to severe COVID-19 disease.

Limitations

The phase 1 and 2 results presented here were based off of small sample sizes, so p-values shown cannot support powerful conclusions. While neutralizing antibody titer were used as a correlate of protection here, no true correlate of protection against SARS-CoV-2 has yet been defined. A neutralizing antibody assay was used here instead of a live virus neutralization assay due to logistical constraints, and no study of T-cell immunity was performed. The trial participants were quite a homogenous population, mostly of Han ethnicity. Further analysis will need to be performed on a more diverse population. Finally, only short-term safety and immunogenicity data is presented here, with further results to come.

Value added

First results published on phase 1/2 trial data regarding the safety and immunogenicity of an inactivated SARS-CoV-2 vaccine (CoronaVac) in a population of older adults.

This review was posted on: 26 February 2021