A randomized, double-blind phase I clinical trial of two recombinant dimeric RBD COVID-19 vaccine candidates: Safety, reactogenicity and immunogenicity.
Обработка статьи · этапы, ошибки и управление
Ошибки и ограничения
История · было → стало
Состояние обновляется каждые 5 секунд, пока блок открыт. Процент показывается только там, где известен объём работы. Пауза останавливает продолжение этапа; текущий запрос к источнику может завершиться.
Pérez-Rodríguez Sonia, de la Caridad Rodríguez-González Meiby, Ochoa-Azze Rolando, Climent-Ruiz Yanet, Alberto González-Delgado Carlos, Paredes-Moreno Beatriz, Valenzuela-Silva Carmen, Rodríguez-Noda Laura, Perez-Nicado Rocmira, González-Mugica Raúl, Martínez-Pérez Marisel, Sánchez-Ramírez Belinda, Hernández-García Tays, Díaz-Machado Alina, Tamayo-Rodríguez Maura, Martín-Trujillo Alis, Rubino-Moreno Jorman, Suárez-Batista Anamary, Dubed-Echevarría Marta, Teresa Pérez-Guevara María, Amoroto-Roig Mayté, Chappi-Estévez Yanet, Bergado-Báez Gretchen, Pi-Estopiñán Franciscary, Chen Guang-Wu, Valdés-Balbín Yury, García-Rivera Dagmar, Verez-Bencomo Vicente
Аннотация
METHODS: We performed a randomized, double-blind, phase I clinical trial in the National Centre of Toxicology in Havana. Sixty Cuban volunteers aged 19-59 years were randomized into three groups (20 subjects each): 1) FINLAY-FR-1 (50 µg d-RBD plus outer membrane vesicles from N. meningitidis); 2) FINLAY-FR-1A-50 (50 µg d-RBD, three doses); 3) FINLAY-FR-1A-25 (25 µg d-RDB, three doses). The FINLAY-FR-1 group was randomly divided to receive a third dose of the same vaccine candidate (homologous schedule) or FINLAY-FR-1A-50 (heterologous schedule). The primary outcomes were safety and reactogenicity. The secondary outcome was vaccine immunogenicity. Humoral response at baseline and following each vaccination was evaluated using live-virus neutralization test, anti-RBD IgG ELISA and in-vitro neutralization test of RBD:hACE2 interaction.
RESULTS: Most adverse events were of mild intensity (63.5%), solicited (58.8%), and local (61.8%); 69.4% with causal association with vaccination. Serious adverse events were not found. The FINLAY-FR-1 group reported more subjects with adverse events than the other two groups. After the third dose, anti-RBD seroconversion was 100%, 94.4% and 90% for the FINLAY-FR-1, FINLAY-FR-1A-50 and FINLAY-FR-1A-25 respectively. The in-vitro inhibition of RBD:hACE2 interaction increased after the second dose in all formulations. The geometric mean neutralizing titres after the third dose rose significantly in the group vaccinated with FINLAY-FR-1 with respect to the other formulations and the COVID-19 Convalescent Serum Panel. No differences were found between FINLAY-FR-1 homologous or heterologous schedules.
CONCLUSIONS: Vaccine candidates were safe and immunogenic, and induced live-virus neutralizing antibodies against SARS-CoV-2. The highest values were obtained when outer membrane vesicles were used as adjuvant.
TRIAL REGISTRY: https://rpcec.sld.cu/en/trials/RPCEC00000338-En.