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

Autor:	Hernández-Bernal F; Centre for Genetic Engineering and Biotechnology, P.O. Box 6162, Havana, Cuba., Ricardo-Cobas MC; 'Saturnino Lora' Hospital, P.O. Box 90100, Santiago de Cuba, Cuba., Martín-Bauta Y; Centre for Genetic Engineering and Biotechnology, P.O. Box 6162, Havana, Cuba., Navarro-Rodríguez Z; 'Saturnino Lora' Hospital, P.O. Box 90100, Santiago de Cuba, Cuba., Piñera-Martínez M; 'Saturnino Lora' Hospital, P.O. Box 90100, Santiago de Cuba, Cuba., Quintana-Guerra J; Centre for Genetic Engineering and Biotechnology, P.O. Box 6162, Havana, Cuba., Urrutia-Pérez K; Centre for Genetic Engineering and Biotechnology, P.O. Box 6162, Havana, Cuba., Urrutia-Pérez K; Centre for Genetic Engineering and Biotechnology, P.O. Box 6162, Havana, Cuba., Chávez-Chong CO; Institute of Cybernetics, Mathematics and Physics, Havana, Cuba., Azor-Hernández JL; Institute of Cybernetics, Mathematics and Physics, Havana, Cuba., Rodríguez-Reinoso JL; Centre for Genetic Engineering and Biotechnology, P.O. Box 6162, Havana, Cuba., Lobaina-Lambert L; 'Saturnino Lora' Hospital, P.O. Box 90100, Santiago de Cuba, Cuba., Colina-Ávila E; 'Saturnino Lora' Hospital, P.O. Box 90100, Santiago de Cuba, Cuba., Bizet-Almeida J; 'Saturnino Lora' Hospital, P.O. Box 90100, Santiago de Cuba, Cuba., Rodríguez-Nuviola J; 'Saturnino Lora' Hospital, P.O. Box 90100, Santiago de Cuba, Cuba., Del Valle-Piñera S; 'Saturnino Lora' Hospital, P.O. Box 90100, Santiago de Cuba, Cuba., Ramírez-Domínguez M; 'Saturnino Lora' Hospital, P.O. Box 90100, Santiago de Cuba, Cuba., Tablada-Ferreiro E; 'Saturnino Lora' Hospital, P.O. Box 90100, Santiago de Cuba, Cuba., Alonso-Valdés M; Centre for Genetic Engineering and Biotechnology, P.O. Box 6162, Havana, Cuba., Lemos-Pérez G; Centre for Genetic Engineering and Biotechnology, P.O. Box 6162, Havana, Cuba., Guillén-Nieto GE; Centre for Genetic Engineering and Biotechnology, P.O. Box 6162, Havana, Cuba., Palenzuela-Díaz A; Immunoassay Centre, Havana, Cuba., Noa-Romero E; Civilian Defense Scientific Research Centre, San José de las Lajas, Mayabeque, Cuba., Limonta-Fernández M; Centre for Genetic Engineering and Biotechnology, P.O. Box 6162, Havana, Cuba., Fernández-Ávila JM; 'Saturnino Lora' Hospital, P.O. Box 90100, Santiago de Cuba, Cuba., Ali-Mros NA; 'Saturnino Lora' Hospital, P.O. Box 90100, Santiago de Cuba, Cuba., Del Toro-Lahera L; 'Saturnino Lora' Hospital, P.O. Box 90100, Santiago de Cuba, Cuba., Remedios-Reyes R; 'Saturnino Lora' Hospital, P.O. Box 90100, Santiago de Cuba, Cuba., Ayala-Ávila M; Centre for Genetic Engineering and Biotechnology, P.O. Box 6162, Havana, Cuba., Muzio-González VL; Centre for Genetic Engineering and Biotechnology, P.O. Box 6162, Havana, Cuba.
Jazyk:	angličtina
Zdroj:	EClinicalMedicine [EClinicalMedicine] 2022 Apr; Vol. 46, pp. 101383. Date of Electronic Publication: 2022 Apr 09.
DOI:	10.1016/j.eclinm.2022.101383
Abstrakt:	Background: Multiple vaccine candidates against COVID-19 are currently being evaluated. We evaluate the safety and immunogenicity protein of a novel SARS-CoV-2 virus receptor-binding domain (RBD) vaccine. Methods: A phase 1-2, randomised, double-blind, placebo-controlled trial was carried out in "Saturnino Lora" Hospital, Santiago de Cuba, 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 (1:1:1, in blocks) to three groups: placebo, 25 µg and 50 µg RBD vaccine (Abdala). The product was administered intramuscularly, 0·5 mL in the deltoid region. During the first phase, two immunization schedules were studied: 0-14-28 days (short) and 0-28-56 days (long). In phase 2, only the short schedule was evaluated. The organoleptic characteristics and presentations of vaccine and placebo were identical. All participants (subjects, clinical researchers, statisticians, laboratory technicians, and monitors) remained masked during the study period. The main endpoints were safety and the proportion of subjects with seroconversion of anti-RBD IgG antibodies, analysed by intention to treat and per protocol, respectively. The trial is registered with the Cuban Public Registry of Clinical Trials, RPCEC00000346. Findings: Between Dec 7, 2020, and Feb 9, 2021, 792 subjects were included; 132 (66 in each vaccination schedule, divided into 22 for each group) in phase 1, and 660 (220 in each group plus 66 from the short scheme of phase 1) in phase 2. The product was well tolerated. No severe adverse events were reported. During phase 1, the incidence of adverse events in the 25 µg, 50 µg, and placebo arms for the short schedule were 6/22 (27·3%), 6/22 (27·3%), 3/22 (13·6%), respectively, and for the long schedule were 8/22 (36·4%), 9/22 (40·9%), 4/22 (18·2%), respectively. In phase 2, adverse reactions were reported by 53/242 (21·9%), 75/242 (31·0%) and 41/242 (16·9%) participants in the 25 µg, 50 µg, and placebo group, respectively. Adverse reactions were minimal, mostly mild, and from the injection site, which resolved in the first 24-48 hours. In phase 1, seroconversion at day 56 was seen in 95·2% of the participants (20/21) in the 50 μg group, 81% (17/21) in the 25 μg group, and none in the placebo group (0/22). For the long schedule, seroconversion at day 70 was seen in 100% of the participants (21/21) in the 50 μg group, 94·7% (18/19) in the 25 μg group, and none in the placebo group (0/22). In phase 2, seroconversion of anti-RBD IgG antibodies at day 56 was seen in 89·2% of the participants in the 50 μg group (214/240; 95% CI 84·5-92·82), 77·7% in the 25 μg group (185/238; 72·0-82·9) and 4·6% in the placebo group (11/239; 2·3-8·1). Compared with the placebo arm, the differences in the proportion of participants with seroconversion were 73·1% (95% CI 66·8-79·5) and 84·6% (79·4-89·7) in the 25 μg and 50 μg groups, respectively. The seroconversion rate in the 50 μg group was significantly higher than in the 25 μg group (p=0·0012). Interpretation: The Abdala vaccine was safe, well tolerated, and induced humoral immune responses against SARS-CoV-2. These results, in the context of the emergency COVID-19 pandemic, support the 50 μg dose, applied in a 0-14-28 days schedule, for further clinical trials to confirm vaccine efficacy. Funding: Centre for Genetic Engineering and Biotechnology (CIGB), Havana, Cuba. Competing Interests: Authors FHB, YMB, JQG, KaUP, KlUP, JLRR, MAV, MLF, GEGN, GLP, MAA, and VLMG, are employees of the Centre for Genetic Engineering and Biotechnology, Havana Network, where Abdala vaccine active ingredient is produced and the formulation was developed. The remaining authors have no conflict of interests. No honoraria, consulting fees or payments for seminar presentations, speeches or appearances have been received by any of the authors. (© 2022 The Author(s).)
Databáze:	MEDLINE
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