Sinovac’s coronavirus disease 2019 (COVID-19) vaccine was well tolerated and moderately immunogenic in healthy adults, according to a study published in The Lancet Infectious Diseases.
Investigators conducted a phase 1/2 randomized, double-blind, placebo-controlled trial (ClinicalTrials.gov, NCT04352608) to test the safety, immunogenicity, and tolerability of CoronaVac (Sinovac Life Sciences, Beijing, China), an inactivated vaccine candidate against COVID-19 containing inactivated severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Healthy adults aged 18 to 59 years were enrolled in phase 1 (n=143) and phase 2 (n=600) trials.
In the phase 1 trial, patients were separated into 2 vaccination cohorts: the days 0 and 14 and the days 0 and 28. Within each cohort, the first 36 patients were assigned to the low-dose vaccine block (3 μg per 0.5 mL of aluminum hydroxide diluent per dose) and the next 36 patients were assigned to the high-dose vaccine block (6 μg per 0.5 mL of aluminum hydroxide diluent per dose). Within each block, participants were randomly assigned (2:1) to receive either 2 doses of the vaccine or 2 doses of placebo.
In the days 0 and 14 cohort, adverse reactions occurred in 7 of 24 (29%) participants in the low-dose group, 9 of 24 (38%) participants in the high-dose group, and 2 of 24 (8%) participants in the placebo group. In the days 0 and 28 cohort, adverse reactions occurred in 3 of 24 (13%) participants in the low-dose group, 4 of 24 (17%) participants in the high-dose group, and 13 of 23 (13%) participants in the placebo group. In the days 0 and 14 cohort, seroconversion of neutralizing antibodies was observed on day 14 in 11 of 24 low-dose participants, 12 of 24 high-dose participants, and 0 of 24 placebo participants. In the days 0 and 28 cohort, seroconversion was observed on day 28 in 20 of 24 (83%) low-dose participants, 19 of 24 (79%) high-dose participants, and 1 of 24 (4%) placebo participants.
In the phase 2 trial, patients were also separated into the same vaccination cohort as the phase 1 trial. Investigators randomized participants in a 2:2:1 fashion into either 2 doses of low-dose vaccine, high-dose vaccine, or placebo. The primary safety endpoint was adverse reactions within 28 days after injection. The primary immunogenic outcome was seroconversion rates of neutralizing antibodies.
In the 0 to 14 days cohort, adverse reactions occurred in 40 of 120 (33%) participants in the low-dose group, 42 of 120 (35%) participants in the high-dose group, and 13 of 60 (22%) participants in the placebo group. Seroconversion was observed in 109 of 118 (92%) of the low-dose group, 117 of 119 (98%) in the high-dose group, and 2 of 60 (3%) in the placebo group. In the days 0 to 28 cohort adverse reactions occurred in 23 of 120 (19%) participants in the low-dose group, 23 of 120 (19%) participants in the high-dose group, and 11 of 60 (18%) participants in the placebo group. Seroconversion occurred in 114 of 117 (97%), 118 of 118 (100%) and 0 of 59, in the low-dose, high-dose, and placebo groups.
Investigators report that both concentrations and schedules were well-tolerated and moderately immunogenic in healthy adults. However, they did not assess T-cell responses in phase 2 and did not include participants from more susceptible risk groups. Other limitations included the lack of support for powerful statistical conclusions for calculated P values, low T-cell responses measured by ELISpot in patients receiving the vaccine, and lack of inclusion of immune reactions mediated by CD8 cells.
These results concerning safety, immunogenicity, and production capacity indicate that “CoronaVac was well-tolerated and induced humoral responses against SARS-CoV-2,” said investigators. Investigators added that these results support the emergency use approval of this vaccine in China. The 3 μg dose of CoronaVac is the suggested dose for efficacy assessment in future phase 3 trials.
Disclosure: Several study authors declared affiliations with the pharmaceutical industry. Please see the original reference for a full list of authors’ disclosures.
Zhang Y, Zeng G, Pan H, et al. Safety, tolerability, and immunogenicity of an inactivated SARS-CoV-2 vaccine in healthy adults aged 18-59 years: a randomised, double-blind, placebo-controlled, phase 1/2 clinical trial. Lancet Infect Dis. Published online November 17, 2020. doi: 10.1016/S1473-3099(20)30843-4.