1. A randomized, double-blind phase I clinical trial of two recombinant dimeric RBD COVID-19 vaccine candidates: Safety, reactogenicity and immunogenicity
- Author
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Franciscary Pi-Estopinan, Jorman Rubino-Moreno, Mayte Amoroto-Roig, Maria Teresa Perez-Guevara, Yury Valdés-Balbín, Laura M. Rodríguez-Noda, Marisel Martinez-Perez, Meiby de la Caridad Rodriguez-Gonzalez, Carmen M Valenzuela-Silva, Dagmar García-Rivera, Rolando Ochoa-Azze, Maura Tamayo-Rodriguez, Raul Gonzalez-Mugica, Vicente Verez-Bencomo, Yanet Chappi-Estevez, Yanet Climent-Ruiz, Belinda Sanchez-Ramirez, Beatriz Paredes-Moreno, Anamary Suarez-Batista, Gretchen Bergado-Baez, Tays Hernandez-Garcia, Alina Díaz-Machado, Alis Martín-Trujillo, Sonia Pérez-Rodríguez, Rocmira Perez-Nicado, Guang-Wu Chen, Marta Dubed-Echevarría, and Carlos A. González-Delgado
- Subjects
Adult ,medicine.medical_specialty ,COVID-19 Vaccines ,medicine.medical_treatment ,Phases of clinical research ,Antibodies, Viral ,Gastroenterology ,Young Adult ,Immunogenicity, Vaccine ,Double-Blind Method ,Internal medicine ,medicine ,Humans ,Seroconversion ,Adverse effect ,COVID-19 Serotherapy ,Reactogenicity ,biology ,General Veterinary ,General Immunology and Microbiology ,SARS-CoV-2 ,business.industry ,Immunogenicity ,Immunization, Passive ,Public Health, Environmental and Occupational Health ,COVID-19 ,Middle Aged ,Antibodies, Neutralizing ,Vaccination ,Infectious Diseases ,Spike Glycoprotein, Coronavirus ,biology.protein ,Molecular Medicine ,Antibody ,business ,Adjuvant - Abstract
BackgroundThe 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 1 clinical trial of two COVID-19 vaccine candidates based on recombinant dimeric RBD (d-RBD).MethodsWe 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 mcg d-RBD plus outer membrane vesicles from N. meningitidis); 2) FINLAY-FR-1A-50 mcg d-RBD (three doses); 3) FINLAY-FR-1A-25 mcg 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 of 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.ResultsMost 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 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.ConclusionsVaccine 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 registryhttps://rpcec.sld.cu/en/trials/RPCEC00000338-En
- Published
- 2022
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