Journal Article

A randomized, double-blind phase I clinical trial of two recombinant dimeric RBD COVID-19 vaccine candidates: Safety, reactogenicity and immunogenicity

Perez-Nicado, Rocmira, Valdés-Balbín, Yury, Teresa Pérez-Guevara, María, Bergado-Báez, Gretchen, Alberto González-Delgado, Carlos, Chappi-Estévez, Yanet, Martínez-Pérez, Marisel, Hernández-García, Tays, Verez-Bencomo, Vicente, Valenzuela-Silva, Carmen, Ochoa-Azze, Rolando, García-Rivera, Dagmar, González-Mugica, Raúl, Dubed-Echevarría, Marta, de la Caridad Rodríguez-González, Meiby, Martín-Trujillo, Alis, Pérez-Rodríguez, Sonia, Pi-Estopiñán, Franciscary, Rubino-Moreno, Jorman, Rodríguez-Noda, Laura, Díaz-Machado, Alina, Climent-Ruiz, Yanet, Sánchez-Ramírez, Belinda, Paredes-Moreno, Beatriz, Suárez-Batista, Anamary, Amoroto-Roig, Mayté, Tamayo-Rodríguez, Maura, Chen, Guang-Wu

2022

Overview

•Dimeric-RBD vaccines against SARS-CoV-2.•New adjuvant for COVID-19 vaccines.•Safety and immunogenicity of homologous and heterologous COVID-19 vaccination schedules.•Dimeric-RBD vaccines were safe and immunogenic, and induced live-virus neutralizing antibodies against SARS-CoV-2. 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). 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. 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. 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.

• Publisher: Elsevier Ltd,Elsevier Limited
• Subject: Adjuvants / Adult / Adverse events / Allergy and Immunology / Antibodies / Antibodies, Neutralizing / Antibodies, Viral / Antigens / blood serum / Clinical trials / Coronavirus infection / Coronaviruses / COVID-19 / COVID-19 - prevention & control / COVID-19 - therapy / COVID-19 infection / COVID-19 Serotherapy / COVID-19 vaccines / COVID-19 Vaccines - adverse effects / Dimers / Double-Blind Method / Double-blind studies / Enzyme-linked immunosorbent assay / Health surveillance / Homology / Humans / humoral immunity / Immune response (humoral) / Immunization schedule / Immunization, Passive / Immunogenicity / Immunogenicity, Vaccine / Immunoglobulin G / Immunology / Immunopotentiator / In vitro methods and tests / Medical screening / Membrane vesicles / Membranes / Middle Aged / Neutralization / neutralization tests / Neutralizing / Neutralizing antibodies / Proteins / Safety / SARS-CoV-2 / Schedules / Seroconversion / Severe acute respiratory syndrome coronavirus 2 / Spike Glycoprotein, Coronavirus / Spike protein / Toxicology / vaccination / Vaccines / Vesicles / Viruses / Young Adult