Article
作者: Valera-Fernández, Rodrigo ; Hernández-Garcia, Tays ; Morales-Ruano, Susana ; González-Mugica, Raúl ; Garrido-Arteaga, Raine ; Alfaro-Guzmán, Ainadis ; Fontanies-Fernández, Marcos ; Garcés-Hechavarría, Aniurka ; Palenzuela-Diaz, Ariel ; Valdés-Balbín, Yury ; Boggiano-Ayo, Tammy ; Sanchez-Ramirez, Belinda ; Bergado-Baez, Gretchen ; Pérez-Rodríguez, Suzel ; Ontivero-Pino, Ivis ; Rodríguez, Misladys ; Santana-Mederos, Darielys ; García-Montero, Majela ; Cardoso-SanJorge, Félix ; Rodríguez-Noda, Laura ; Perez-Perez, Alina ; Paredes-Moreno, Beatriz ; Verdecia-Sánchez, Leslyhana ; Zulueta-Pérez, Lilian ; Arteaga-García, Amaylid ; Galano-Frutos, Evelyn ; Amoroto, Maité ; Pi-Estopiñán, Franciscary ; Dubed-Echevarría, Marta ; Chen, Guang-Wu ; Espino-Rojas, Niurka Tamara ; Muñoz, Yaima ; Ojito-Magaz, Eduardo ; Díaz-Hernández, Marianniz ; Rodríguez-Castillo, Pedro Gabriel ; Cubas-Curbelo, Mailin ; Lora-García, Janet ; Ávila-Cabreja, José Alejandro ; Acevedo-Martínez, Yosmel ; Rivera, Daniel G. ; Orosa-Vázquez, Ivette ; Santos-Vega, Bertha Leysi ; Valenzuela-Silva, Carmen ; Cruz-Sui, Otto ; Acosta-Martinez, Mario Alejandro ; Domínguez-Pentón, Yeney Regla ; Martínez-Bedoya, Dayle ; Noa-Romero, Enrique ; Mendoza-Hernández, Ivis ; Guillén-Obregón, Berta ; Vérez-Bencomo, Vicente ; Quintero-Moreno, Lauren ; García-López, Elena ; Martínez-Rivera, Roselyn ; Medinas-Santos, Gloria Margarita ; García-Rivera, Dagmar ; Martínez-Pérez, Marisel ; Espi-Ávila, Jennifer ; Baro-Roman, Gerardo ; Doroud, Delaram ; Reyes-Matienzo, Radamet ; Ramírez-Gonzalez, Ubel ; Estoque-Cabrera, Solangel ; Climent-Ruiz, Yanet ; Brito-Pascual, Idalmis ; García-Vega, Yanelda ; Pérez-Guevara, María Teresa ; García-Carmenate, Mayra ; Fernandez-Castillo, Sonsire ; Gómez-Maceo, Yanet ; Morffi-Cinta, Irania ; Sarda-Rodriguez, Ileana Luisa ; Rodriguez-González, Meybis ; Enriquez-Puertas, Juliet ; Biglari, Alireza ; Toledo-Romani, María Eugenia ; Medina-Nápoles, Maite ; Coviella-Artime, José Manuel
BACKGROUND:SOBERANA 02 has been evaluated in phase I and IIa studies comparing homologous versus heterologous schedule (this one, including SOBERANA Plus). Here, we report results of immunogenicity, safety, and reactogenicity of SOBERANA 02 in a two- or three-dose heterologous scheme in adults.
METHOD:Phase IIb was a parallel, multicenter, adaptive, double-blind, randomized, and placebo-controlled trial. Subjects (n = 810) aged 19-80 years were randomized to receive two doses of SARS-CoV-2 RBD conjugated to tetanus toxoid (SOBERANA 02) and a third dose of dimeric RBD (SOBERANA Plus) 28 days apart; two production batches of active ingredients of SOBERANA 02 were evaluated. Primary outcome was the percentage of seroconverted subjects with ≥4-fold the anti-RBD immunoglobulin G (IgG) concentration. Secondary outcomes were safety, reactogenicity, and neutralizing antibodies.
FINDINGS:Seroconversion rate in vaccinees was 76.3% after two doses and 96.8% after the third dose of SOBERANA Plus (7.3% in the placebo group). Neutralizing IgG antibodies were detected against D614G and variants of concern (VOCs) Alpha, Beta, Delta, and Omicron. Specific, functional antibodies were detected 7-8 months after the third dose. The frequency of serious adverse events (AEs) associated with vaccination was very low (0.1%). Local pain was the most frequent AE.
CONCLUSIONS:Two doses of SOBERANA 02 were safe and immunogenic in adults. The heterologous combination with SOBERANA Plus increased neutralizing antibodies, detectable 7-8 months after the third dose.
TRIAL REGISTRY:https://rpcec.sld.cu/trials/RPCEC00000347 FUNDING: This work was supported by Finlay Vaccine Institute, BioCubaFarma, and the Fondo Nacional de Ciencia y Técnica (FONCI-CITMA-Cuba, contract 2020-20).