María Eugenia Toledo-Romani, Mayra García-Carmenate, Leslyhana Verdecia-Sánchez, Suzel Pérez-Rodríguez, Meybis Rodriguez-González, Carmen Valenzuela-Silva, Beatriz Paredes-Moreno, Belinda Sanchez-Ramirez, Raúl González-Mugica, Tays Hernández-Garcia, Ivette Orosa-Vázquez, Marianniz Díaz-Hernández, María Teresa Pérez-Guevara, Juliet Enriquez-Puertas, Enrique Noa-Romero, Ariel Palenzuela-Diaz, Gerardo Baro-Roman, Ivis Mendoza-Hernández, Yaima Muñoz, Yanet Gómez-Maceo, Bertha Leysi Santos-Vega, Sonsire Fernandez-Castillo, Yanet Climent-Ruiz, Laura Rodríguez-Noda, Darielys Santana-Mederos, Yanelda García-Vega, Guang-Wu Chen, Delaram Doroud, Alireza Biglari, Tammy Boggiano-Ayo, Yury Valdés-Balbín, Daniel G. Rivera, Dagmar García-Rivera, Vicente Vérez-Bencomo, Mailin Cubas-Curbelo, Pedro Gabriel Rodríguez-Castillo, Yosmel Acevedo-Martínez, Solangel Estoque-Cabrera, José Alejandro Ávila-Cabreja, Ainadis Alfaro-Guzmán, Lilian Zulueta-Pérez, Niurka Tamara Espino-Rojas, Gloria Margarita Medinas-Santos, Ileana Luisa Sarda-Rodriguez, Mario Alejandro Acosta-Martinez, Radamet Reyes-Matienzo, José Manuel Coviella-Artime, Irania Morffi-Cinta, Marisel Martínez-Pérez, Rodrigo Valera-Fernández, Aniurka Garcés-Hechavarría, Dayle Martínez-Bedoya, Raine Garrido-Arteaga, Félix Cardoso-SanJorge, Ubel Ramírez-Gonzalez, Lauren Quintero-Moreno, Ivis Ontivero-Pino, Roselyn Martínez-Rivera, Berta Guillén-Obregón, Janet Lora-García, Maite Medina-Nápoles, Jennifer Espi-Ávila, Marcos Fontanies-Fernández, Yeney Regla Domínguez-Pentón, Gretchen Bergado-Baez, Franciscary Pi-Estopiñán, Eduardo Ojito-Magaz, Misladys Rodríguez, Otto Cruz-Sui, Majela García-Montero, Marta Dubed-Echevarría, Elena García-López, Evelyn Galano-Frutos, Alina Perez-Perez, Susana Morales-Ruano, Idalmis Brito-Pascual, Maité Amoroto, and Amaylid Arteaga-García
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.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.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.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.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).