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Vaccine
. 2022 Feb 8;S0264-410X(22)00161-X.
doi: 10.1016/j.vaccine.2022.02.029. Online ahead of print.
A randomized, double-blind phase I clinical trial of two recombinant dimeric RBD COVID-19 vaccine candidates: Safety, reactogenicity and immunogenicity
Sonia Pérez-Rodríguez 1 , Meiby de la Caridad Rodríguez-González 2 , Rolando Ochoa-Azze 3 , Yanet Climent-Ruiz 2 , Carlos Alberto González-Delgado 1 , Beatriz Paredes-Moreno 2 , Carmen Valenzuela-Silva 4 , Laura Rodríguez-Noda 2 , Rocmira Perez-Nicado 2 , Raúl González-Mugica 2 , Marisel Martínez-Pérez 2 , Belinda Sánchez-Ramírez 5 , Tays Hernández-García 5 , Alina Díaz-Machado 1 , Maura Tamayo-Rodríguez 1 , Alis Martín-Trujillo 1 , Jorman Rubino-Moreno 1 , Anamary Suárez-Batista 6 , Marta Dubed-Echevarría 6 , María Teresa Pérez-Guevara 6 , Mayté Amoroto-Roig 7 , Yanet Chappi-Estévez 7 , Gretchen Bergado-Báez 5 , Franciscary Pi-Estopiñán 5 , Guang-Wu Chen 8 , Yury Valdés-Balbín 2 , Dagmar García-Rivera 2 , Vicente Verez-Bencomo 2
Affiliations
- PMID: 35164986
- DOI: 10.1016/j.vaccine.2022.02.029
Abstract
Background: The Receptor Binding Domain (RBD) of the SARS-CoV-2 spike protein is the target for many COVID-19 vaccines. Here we report results for phase I clinical trial of two COVID-19 vaccine candidates based on recombinant dimeric RBD (d-RBD).
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.
Keywords: Adjuvants; COVID-19; Coronavirus infection; Immunization schedule; Immunopotentiator; Neutralizing antibodies; SARS-CoV-2; Vaccines.