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

•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 Bindi...

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Vydáno v:	Vaccine Ročník 40; číslo 13; s. 2068 - 2075
Hlavní autoři:	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
Médium:	Journal Article
Jazyk:	angličtina
Vydáno:	Netherlands Elsevier Ltd 18.03.2022 Elsevier Limited
Témata:	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 Cuba COVID-19 Immunopotentiator SARS-CoV-2 Coronavirus infection Neutralizing antibodies Immunization schedule Adjuvants Vaccines
ISSN:	0264-410X, 1873-2518, 1873-2518
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Shrnutí:	•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.
Bibliografie:	ObjectType-Article-1 SourceType-Scholarly Journals-1 ObjectType-Feature-2 content type line 14 content type line 23 ObjectType-Undefined-3 Joint first authors.
ISSN:	0264-410X 1873-2518 1873-2518
DOI:	10.1016/j.vaccine.2022.02.029