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Background: The pandemic of COVID-19 raised the urgent need of safe and efficacious vaccines against SARS-CoV-2. We evaluated the efficacy and safety of a new SARS-CoV-2 virus receptor-binding domain (RBD) vaccine. Methods: A phase 3, multicentre, randomised, double-blind, placebo-controlled trial was carried out at 18 clinical sites in three provinces of the south-eastern region of Cuba. Subjects (healthy or those with controlled chronic diseases) aged between 19 and 80 years, who gave written informed consent were eligible. Subjects were randomly assigned (1:1, in blocks) to two groups: placebo, and 50 mcg RBD vaccine (Abdala). The product was administered intramuscularly, 0.5 mL in the deltoid region, in a three dose immunization schedule at 0-14-28 days. The organoleptic characteristics and presentations of vaccine and placebo were identical. All participants (subjects, clinical researchers, statisticians, laboratory technicians, and monitors) remained blinded during the study period. The main endpoint was to evaluate the efficacy of the Abdala vaccine in the prevention of symptomatic COVID-19. The trial is registered with the Cuban Public Registry of Clinical Trials, RPCEC00000359. Findings: Between March 22 to April 03, 2021, 48290 subjects were included (24144 and 21146 in the placebo and Abdala groups, respectively). The product was well tolerated. No severe adverse events with demonstrated cause-effect relationship attributable to vaccine were reported. The incidence of adverse reactions in the placebo and Abdala vaccine arms were 446/24144 (1.9%) and 615/24146 (2.5%), respectively. Adverse reactions were mostly mild, and from the injection site, which resolved in the first 24-48 hours. The Abdala vaccine efficacy against symptomatic COVID-19 was 92.28% (95% CI 85.74-95.82). In the case of mild/moderate disease the vaccine efficacy was 91.96% (84.69-95.78) and 94.46% (58.52-99.28) for the severe forms (serious/critical disease). There were five critical patients (of which four died), all in the placebo group, indicating that Abdala vaccine efficacy for both conditions was of 100%. Interpretation: The Abdala vaccine was safe, well tolerated, and highly effective, fulfilling the WHO target product profile for COVID-19 vaccines. Funding: Centre for Genetic Engineering and Biotechnology (CIGB), Havana, Cuba.

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AimTo evaluate the safety and immunogenicity of a SARS-CoV-2 recombinant spike protein vaccine (Abdala), administered intramuscularly in different strengths and vaccination schedules.MethodA phase 1-2, randomized, double-blind, placebo-controlled trial was done. Subjects were randomly distributed in 3 groups: placebo, 25 and 50µg RBD. The product was applied intramuscularly, 0.5 mL in the deltoid region. During the first phase, two immunization schedules were studied: short (0-14-28 days) and long (0-28-56 days). In phase 2, only the short scheme was evaluated. The main endpoints were: safety and proportion of subjects with seroconversion of anti-RBD IgG antibodies to SARS-CoV-2. Blood samples were collected in several points according to the corresponding vaccination schedule to determine the level of RBD-specific IgG antibodies (seroconversion rates and geometric mean of the titers), the percentage of inhibition of RBD-ACE-2 binding and levels of neutralizing antibodies.ResultsThe product was well tolerated. Severe adverse events were not reported. Adverse reactions were minimal, mostly mild and local (from the injection site), resolved in the first 24-48 hours without medication. In phase 1, at day 56 (28 days after the third dose of the short vaccination schedule, 0-14-28 days) seroconversion of anti-RBD IgG was seen in 95.2 % of the participants (20/21) for the 50μg group and 81 % of the participants (17/21) for the 25μg group, and none in the placebo group (0/22); whereas neutralizing antibodies to SARS-CoV-2 were seen in 80 % of the participants (8/10) for the 50μg group and 94.7% of the participants (18/19) for the 25μg group. For the long schedule, at day 70 (14 days after the third dose) seroconversion of anti-RBD IgG was seen in 100% of the participants (21/21) for the 50μg group and 94.7% of the participants (18/19) for the 25μg group, and none in the placebo group (0/22); whereas neutralizing antibodies to SARS-CoV-2 were seen in 95 % of the participants (19/20) for the 50μg group and 93.8% of the participants (15/16) for the 25μg group In phase 2, at day 56 seroconversion of anti-RBD IgG was seen in 89.2% of the participants (214/240) for the 50μg group, 77.7% of the participants (185/238) for the 25μg group, and 4.6% in the placebo group (11/239); whereas neutralizing antibodies to SARS-CoV-2 were seen in 97.3% of the participants (146/150) for the 50μg group and 95.1% of the participants (58/61) for the 25μg group.ConclusionAbdala vaccine against SARS-CoV-2 was safe, well tolerated and induced humoral immune responses against SARS-CoV-2 among adults from 19 to 80 years of age.Trial registration / Review protocolRPCEC00000346. Cuban Public Clinical Trial Registry (WHO accepted Primary Registry).Available from: https://rpcec.sld.cu/en/trials/RPCEC00000346-EnInformation about the ethical aspects and IRB approvalThe protocol was approved by the Ethic Committee of the participating hospital and by the Cuban Regulatory Authority (Center for State Control of Drugs, Medical Devices and Equipment).Summary boxCOVID-19 is a serious global health problem. Vaccines are urgently needed to protect humanity. Multiple vaccine candidates are currently being evaluated. The article shows promising safety and immunogenicity results for a vaccine candidate, based on the recombinant RBD subunit of the spike protein.