Safety and efficacy of two immunization schedules with an inactivated SARS-CoV-2 vaccine in adults. A randomized non-inferiority clinical trial.

BackgroundSeveral vaccines have been developed to control the COVID-19 pandemic. CoronaVac(R) (Sinovac Life Sciences), an inactivated SARS-CoV-2 vaccine, has demonstrated safety and immunogenicity in previous studies, preventing severe COVID-19 cases. We further investigated the safety and efficacy of two immunization schedules of CoronaVac(R) in a non-inferiority trial in healthy adults.

MethodsThis is a multi-center and randomized clinical trial. Healthy adults were enrolled at eight centers in Chile. Participants were randomly assigned to two vaccination schedules, receiving two doses with either 14 (0-14) or 28 (0-28) days between each. 2302 participants were vaccinated. The primary safety and efficacy endpoints were solicited adverse events (AE) within 7 days after each dose and compared the number of cases of SARS-CoV-2 infection 14 days after the second dose between schedules, respectively.

FindingsThe most frequent local AE was pain at the injection site, which was less frequent in participants aged [≥]60 years. Other local AEs were reported in less than 5% of participants. The most frequent systemic AEs were headache, fatigue, and myalgia. The remaining AEs were minor allergic reactions and fever. Most AEs were mild and transient. There were no significant differences for local and systemic AE between schedules. No anaphylactic reactions or vaccine-related severe AEs were observed. 58 COVID-19 cases were confirmed, and all but two of them were mild. No differences were observed in protection between schedules.

InterpretationCoronaVac(R) is safe, especially in [≥]60 years-old participants. Both schedules protected against COVID-19 hospitalizations.

FundingMINSAL, Chile, CPC & IMII, Chile.

Research in contextO_ST_ABSEvidence before this studyC_ST_ABSCoronaVac(R) (an inactivated SARS-CoV-2 vaccine) was approved on June 1st, 2021, by the WHO for its use in humans. Sinovac Life Sciences generated this vaccine in China and conducted phase 1/2 trials. Good safety, efficacy, and immunogenicity profiles were reported. The results from this study led to the use of CoronaVac(R) in other countries, such as Brazil, Turkey, and Chile, with phase 3 trials being held on them.

Added-value of this studyThis work compares the safety and efficacy of two immunization schedules with CoronaVac(R), with each dose administrated two or four weeks after the first dose on healthy Chilean adults. To date, no studies showing the safety and efficacy of these two immunization schedules with CoronaVac(R) in healthy adults in a population other than the Chinese have been published. We show that CoronaVac(R) is safe and prevents hospitalization due to COVID-19 in both immunization schedules. No differences were found in the incidence of adverse events between both schedules, and no related severe adverse events were reported. These results give further insight into the immune response induced by CoronaVac(R) and are relevant when deciding on the immunization schedule chosen for vaccination.

Implications of all the available evidenceThe data reported here show that using either immunization schedule with two doses of CoronaVac(R) protects against SARS-CoV-2. The data also indicate that CoronaVac(R) does not induce severe adverse events in either immunization schedule, and the adverse events registered are mild and transient, confirming the safety of this vaccine.