A phase 3, randomised, double-blind, placebo-controlled clinical trial for adult evaluation of the efficacy and safety of a SARS-CoV-2 recombinant spike RBD protein vaccine (ABDALA-3 Study)

Abstract

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.

Efficacy of SARS-CoV-2 vaccines and the dose–response relationship with three major antibodies: a systematic review and meta-analysis of randomised controlled trials

“…Of the 41 053 papers retrieved, 28 eligible efficacy RCTs published in 32 publications were included in this review ( figure 1 ; appendix pp 20–100 ). 19 , 20 , 21 , 22 , 23 , 24 , 25 , 26 , 27 , 28 , 29 , 30 , 31 , 32 , 33 , 34 , 35 , 36 , 37 , 38 , 39 , 40 , 41 , 42 , 43 , 44 , 45 , 46 , 47 , 48 , 49 , 50 A total of 286 915 participants in vaccination groups and 233 236 in placebo groups were involved, with a median follow-up ranging from 1 month to 6 months after last vaccination in individual RCTs. 27 eligible RCTs assessed the efficacy of full vaccination for DNA, mRNA, viral vector, inactivated virus, and recombinant protein vaccines.…”

“…27 RCTs investigated vaccine efficacy against symptomatic infection. 19 , 20 , 21 , 22 , 23 , 24 , 25 , 26 , 28 , 29 , 30 , 31 , 33 , 34 , 35 , 36 , 37 , 38 , 40 , 41 , 43 , 44 , 46 , 47 , 48 , 49 , 50 The combined efficacy was 76·5% (95% CI 69·8–81·7) with high heterogeneity ( I 2 =93·0%, p<0·0001): 67·3% (95% CI 45·8–80·2) for the DNA vaccine, 85·5% (63·5–94·2) for mRNA vaccines, 69·9% (58·2–78·4) for viral vector vaccines, 72·1% (58·9–81·1) for inactivated vaccines, and 76·3% (67·0–82·9) for recombinant protein vaccines ( Figure 2 , Figure 3 ). Vaccine efficacy for preventing symptomatic infection was 78·2% (64·0–86·8) for alpha (B.1.1.7) variants of concern, 33·4% (7·1–52·2) for beta (B.1.351) variants of concern, 73·1% (31·5–89·4) for gamma (P.1) variants of concern, and 67·0% (50·0–78·2) for delta (B.1.617.2) variants of concern.…”

“…13 RCTs assessed the efficacy of vaccination against COVID-19 related death. 21 , 23 , 25 , 27 , 28 , 30 , 31 , 34 , 37 , 41 , 43 , 46 , 48 The combined efficacy was 85·8% (95% CrI 68·7 to 94·6) with modest heterogeneity ( I 2 =3·5%, p=0·94): 85·8% (95% CrI –174·2 to 99·3) for mRNA vaccines, 88·4% (56·8 to 97·9) for viral vector vaccines, 93·5% (–447·4 to 100·0) for inactivated vaccines, and 82·8% (48·3 to 95·6) for recombinant protein vaccines (figures 2, 3).…”

Application of Traditional Vaccine Development Strategies to SARS-CoV-2

“…Based on the reported results, Abdala gained emergency use authorization in Cuba in July 2021 ( 215 ), and by December 2021, cases in Cuba had dropped dramatically ( 216 ). The results of the phase III trial were posted to medRxiv in September 2022, describing the results of a randomized, placebo-controlled, multicenter, double-blind investigation of the Abdala vaccine candidate in 48,000 participants between 22 March and 3 April 2021 ( 217 ). The final results included 42 symptomatic cases of COVID-19 among participants in the placebo condition, compared to only 11 cases among participants who received the vaccine, yielding the reported VE of 92.28% ( 217 ).…”

“…The results of the phase III trial were posted to medRxiv in September 2022, describing the results of a randomized, placebo-controlled, multicenter, double-blind investigation of the Abdala vaccine candidate in 48,000 participants between 22 March and 3 April 2021 ( 217 ). The final results included 42 symptomatic cases of COVID-19 among participants in the placebo condition, compared to only 11 cases among participants who received the vaccine, yielding the reported VE of 92.28% ( 217 ). In terms of secondary endpoints, the VEs were 91.96% against mild/moderate COVID-19, 94.46% against severe COVID-19, and 100% against critical illness and death ( 217 ).…”