Efficacy and safety of an inactivated whole-virion SARS-CoV-2 vaccine (CoronaVac): interim results of a double-blind, randomised, placebo-controlled, phase 3 trial in Turkey

Abstract

Background CoronaVac, an inactivated whole-virion SARS-CoV-2 vaccine, has been shown to be well tolerated with a good safety profile in individuals aged 18 years and older in phase 1/2 trials, and provided a good humoral response against SARS-CoV-2. We present the interim efficacy and safety results of a phase 3 clinical trial of CoronaVac in Turkey.Methods This was a double-blind, randomised, placebo-controlled phase 3 trial. Volunteers aged 18-59 years with no history of COVID-19 and with negative PCR and antibody test results for SARS-CoV-2 were enrolled at 24 centres in Turkey. Exclusion criteria included (but were not limited to) immunosuppressive therapy (including steroids) within the past 6 months, bleeding disorders, asplenia, and receipt of any blood products or immunoglobulins within the past 3 months. The K1 cohort consisted of health-care workers (randomised in a 1:1 ratio), and individuals other than health-care workers were also recruited into the K2 cohort (randomised in a 2:1 ratio) using an interactive web response system. The study vaccine was 3 μg inactivated SARS-CoV-2 virion adsorbed to aluminium hydroxide in a 0•5 mL aqueous suspension. Participants received either vaccine or placebo (consisting of all vaccine components except inactivated virus) intramuscularly on days 0 and 14. The primary efficacy outcome was the prevention of PCR-confirmed symptomatic COVID-19 at least 14 days after the second dose in the per protocol population. Safety analyses were done in the intention-to-treat population. This study is registered with ClinicalTrials.gov (NCT04582344) and is active but no longer recruiting.

Effectiveness of the CoronaVac vaccine in older adults during a gamma variant associated epidemic of covid-19 in Brazil: test negative case-control study

“…A key evidence gap, as raised in the WHO EUL for CoronaVac,11 has been the effectiveness of this vaccine in the elderly population, because this age group was not well represented in Brazilian and Turkish randomised controlled trials 571011. We found that two doses of CoronaVac administered at an average interval of four weeks had an overall effectiveness against symptomatic covid-19 of 47% (39% to 54%) in a population with a mean age of 76 years.…”

“…A preliminary aggregated analysis using weekly times series of covid-19 deaths in Brazil found a relative decrease in mortality among those aged ≥70 years compared with all ages after vaccination with CoronaVac and ChAdOx1 nCov-19,45 suggesting a discernible impact of vaccination on mortality at the population level. Additional investigation is required to determine the duration of protection conferred by CoronaVac 71923…”

“…As of early July 2021 the covid-19 pandemic has been responsible for 3.9 million deaths worldwide,1 with a disproportionately high mortality and morbidity among elderly people 2. A key question is whether the authorised covid-19 vaccines are effective in elderly people, who might have impaired immune responses34 and are underrepresented in randomised controlled trials 567. mRNA and adenovirus vector based vaccines have been shown to be effective against covid-19 in elderly people,89 but evidence on the effectiveness of inactivated vaccines in this population is limited 7101112…”

“…CoronaVac (Sinovac Biotech), an inactivated whole virus vaccine, has been approved by 32 countries and jurisdictions10 and been implemented as part of mass vaccination campaigns in low and middle income countries, many of which are experiencing covid-19 epidemics as a result of the emergence of SARS-CoV-2 variants of concern. Estimates from randomised controlled trials of vaccine efficacy against symptomatic covid-19 of a two dose CoronaVac regimen in healthcare workers and the general population have varied (51% to 84%) 5710. The World Health Organization’s Emergency Use Listing (EUL) procedure approved the use of CoronaVac in early June 2021 but identified an evidence gap for the effectiveness of this vaccine in adults aged ≥60 years 11.…”

Real world effectiveness of covid-19 vaccines

“…Post-introduction vaccine studies provide practitioners and policy makers with the kind of evidence that clinical trials cannot—including real world vaccine effectiveness against multiple clinical outcomes. Two linked studies12 that together examined three covid-19 vaccines, add to mounting evidence that efficacy reported in clinical trials translates well to the real world 34567. The studied vaccines—CoronaVac (Sinovac Biotech), BNT162b2 (Pfizer-BioNTech), and mRNA-1273 (Moderna)—performed well in preventing severe covid-19 and deaths in adults after two doses; a single dose was significantly less effective, and all three vaccines were effective (although demonstrably less so) against milder disease.…”