Article
作者: Valera-Fernández, Rodrigo ; Orosa-Vázquez, Ivette ; Rodríguez-Noda, Laura ; Pérez-Massón, Beatriz ; Teresa Pérez-Guevara, María ; Rojas, Gertrudis ; Ontivero-Pino, Ivis ; Vérez-Bencomo, Vicente ; Muñoz-Morejon, Yaima ; García-López, Elena ; Valdés-Balbín, Yury ; González-Mugica, Raul ; Sánchez-Ramírez, Belinda ; Cruz-Sui, Otto ; Boggiano-Ayo, Tammy ; Mendoza-Hernández, Ivis ; Espi Ávila, Jennifer ; Hernández-García, Tays ; Quintero Moreno, Lauren ; Manuel Coviella-Artime, José ; García-Vega, Yanelda ; Bergado-Baez, Gretchen ; Verdecia-Sánchez, Leslyhana ; Castillo-Quintana, Ismavy ; García-Montero, Majela ; Cardoso-SanJorge, Félix ; Tundidor, Yaima ; Martínez-Pérez, Marisel ; Rodríguez-González, Meiby ; Pérez-Nicado, Rocmira ; Rodríguez-Alvarez, Julián ; Morales-García, Marilin ; Martínez-Bedoya, Dayle ; Gómez-Maceo, Yanet ; Ramírez Gonzalez, Ubel ; Medina Nápoles, Maite ; Arteaga, Amaylid ; Santana-Mederos, Darielys ; Fernandez-Castillo, Sonsire ; Rivera, Daniel G ; Fontanies Fernández, Marcos ; Ojito-Magaz, Eduardo ; García-Rivera, Dagmar ; Valenzuela-Silva, Carmen ; Reyes-Matienzo, Radamet ; Díaz-Hernández, Marianniz ; Climent-Ruiz, Yanet ; Galano-Frutos, Evelyn ; Garrido-Arteaga, Raine ; Morffi-Cinta, Irania ; Baró-Román, Gerardo ; Fraga-Quintero, Anitza ; Noa-Romero, Enrique ; Palenzuela-Díaz, Ariel ; Pi-Estopiñán, Franciscary ; Paredes-Moreno, Beatriz ; Eugenia-Toledo-Romaní, María ; Garcés-Hechavarría, Aniurka ; Guang-Wu-Chen
BACKGROUNDSOBERANA 02 is a COVID-19 vaccine based on SARS-CoV-2 recombinant RBD conjugated to tetanus toxoid (TT). SOBERANA Plus antigen is dimeric-RBD. Here we report safety and immunogenicity from phase I and IIa clinical trials using two-doses of SOBERANA 02 and three-doses (homologous) or heterologous (with SOBERANA Plus) protocols.METHODWe performed an open-label, sequential and adaptive phase I to evaluate safety and explore the immunogenicity of SOBERANA 02 in two formulations (15 or 25 μg RBD-conjugated to 20 μg of TT) in 40 subjects, 19-59-years-old. Phase IIa was open-label including 100 volunteers 19-80-years, receiving two doses of SOBERANA 02-25 μg. In both trials, half of volunteers were selected to receive a third dose of the corresponding SOBERANA 02 and half received a heterologous dose of SOBERANA Plus. Primary outcome was safety. The secondary outcome was immunogenicity evaluated by anti-RBD IgG ELISA, molecular neutralization of RBD:hACE2 interaction, live-virus-neutralization and specific T-cells response.RESULTSThe most frequent adverse event (AE) was local pain, other AEs had frequencies ≤ 5%. No serious related-AEs were reported. Phase IIa confirmed the safety in 60 to 80-years-old subjects. In phase-I SOBERANA 02-25 µg elicited higher immune response than SOBERANA 02-15 µg and progressed to phase IIa. Phase IIa results confirmed the immunogenicity of SOBERANA 02-25 µg even in 60-80-years. Two doses of SOBERANA02-25 µg elicited an immune response similar to that of the Cuban Convalescent Serum Panel and it was higher after the homologous and heterologous third doses. The heterologous scheme showed a higher immunological response. Anti-RBD IgG neutralized the delta variant in molecular assay, with a 2.5-fold reduction compared to D614G neutralization.CONCLUSIONSSOBERANA 02 was safe and immunogenic in persons aged 19-80 years, eliciting neutralizing antibodies and specific T-cell response. Highest immune responses were obtained in the heterologous three doses protocol.TRIAL REGISTRYhttps://rpcec.sld.cu/trials/RPCEC00000340, https://rpcec.sld.cu/trials/RPCEC00000347.