As the world grapples with the coronavirus disease 2019 (COVID-19) pandemic, scientists are racing to develop an effective and safe vaccine against the causative agent, severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2).
Now, Sinovac Biotech's candidate vaccine, CoronaVac, has been found to induce an immune response in healthy adults aged 18–59 years, 28 days post-vaccination. However, the level of antibodies generated was lower than in people who had recovered from the illness.
The researchers published the trial results in the prestigious medical journal The Lancet, in November 2020. The data, which aimed to determine the efficacy and safety of the candidate COVID-19 vaccine, were from phase 1 and phase 2 clinical trials with a total of 743 participants.
Sinovac is a leading provider of biopharmaceutical products in China. The company developed the CoronaVac vaccine specifically for SARS-CoV-2 CoronaVac is a chemically-inactivated whole SARS-CoV-2 virus vaccine, making it different from the messenger RNA (mRNA) candidate vaccines produced by Moderna and Pfizer.
In the randomized, double-blind, placebo-controlled phase 1 and 2 clinical trials, the researchers enrolled healthy adults between 18 and 59 years old in Suining County of Jiangsu province, China.
In phase 1, the 144 participants were divided into two vaccination groups during screening – the days 0 and 14 vaccination cohort and the days 0 and 28 vaccination cohort. The first 36 participants in each cohort were assigned to block 1, who received a low-dose CoronaVac. Meanwhile, another 36 participants were assigned to block 2, who received a high-dose CoronaVac.
Within each block, the participants were randomly assigned to either two doses of CoronaVac or two doses of placebo.
In the phase 2 trial, 600 participants were separated into a day 0 to 14 vaccination cohort and a day 0 to 28 vaccination cohort. The scientists then randomly assigned the participants with a block size of five to receive two doses of either a low-dose CoronaVac, a high-dose CoronaVac, or a placebo.
The team observed for any adverse effects within 28 days after injection. Further, they tested the seroconversion rates of neutralizing antibodies to live SARS-CoV-2 at day 14 after the last dose in the days 0 and 14 cohorts and at day 28 after the previous dose in the day 0 to 28 cohort.
The scientists conducted the phase 1 trial between April 16 and April 25, 2020, and the phase 2 between May 3 and May 5, 2020.
In the phase 1 trial, seven participants in the first cohort and nine participants in the second experienced adverse reactions.
About 33 percent in the low-dose group and 35 percent in the high-dose group reported unwanted reactions in the second phase of the vaccine trial.
Seroconversion of neutralizing antibodies
Seroconversion of neutralizing antibodies shows if the vaccine had induced an immune response against SARS-CoV-2.
About 50 percent of the participants, who received the shot after 14 days, developed neutralizing antibodies in the trial's first phase. For those who received the second dose after 28 days, 83 percent developed neutralizing antibodies.
In the second phase of the trial, 98 percent of the participants who received the second shot after 14 days developed neutralizing antibodies. Meanwhile, all of those who received the second shot after 28 days had detectable antibodies against SARS-CoV-2.
The researchers concluded that CoronaVac was well-tolerated and triggered humoral responses against SARS-CoV-2, which supported the approval of the vaccine's emergency use in China.
"Our findings show that CoronaVac is capable of inducing a quick antibody response within four weeks of immunization by giving two doses of the vaccine at a 14-day interval," Zhu Fengcai, one of the authors of the paper, said.
"We believe that this makes the vaccine suitable for emergency use during the pandemic," Zhu added.
- Zhang, Y., Zeng, G., Pan, H. et al. (2020). Safety, tolerability, and immunogenicity of an inactivated SARS-CoV-2 vaccine in healthy adults aged 18–59 years: a randomized, double-blind, placebo-controlled, phase 1/2 clinical trial. The Lancet.
- https://doi.org/10.1016/S1473-3099(20)30843-4, https://www.thelancet.com/journals/laninf/article/PIIS1473-3099(20)30843-4/fulltext