Safety, tolerability, and immunogenicity of a SARS-CoV-2 recombinant spike protein vaccine: a randomised, double-blind, placebo-controlled, phase 1-2 clinical trial (ABDALA Study).

ABSTRACT

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 50{micro}g 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 50g group and 81 % of the participants (17/21) for the 25g 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 50g group and 94.7% of the participants (18/19) for the 25g 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 50g group and 94.7% of the participants (18/19) for the 25g 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 50g group and 93.8% of the participants (15/16) for the 25g group In phase 2, at day 56 seroconversion of anti-RBD IgG was seen in 89.2% of the participants (214/240) for the 50g group, 77.7% of the participants (185/238) for the 25g 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 50g group and 95.1% of the participants (58/61) for the 25g 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-En Information 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.