International Journal of Infectious Diseases (Jan 2023)
Open-label phase I/II clinical trial of SARS-CoV-2 receptor binding domain-tetanus toxoid conjugate vaccine (FINLAY-FR-2) in combination with receptor binding domain-protein vaccine (FINLAY-FR-1A) in children
- Rinaldo Puga-Gómez,
- Yariset Ricardo-Delgado,
- Chaumey Rojas-Iriarte,
- Leyanis Céspedes-Henriquez,
- Misleidys Piedra-Bello,
- Dania Vega-Mendoza,
- Noelvia Pestana Pérez,
- Beatriz Paredes-Moreno,
- Meiby Rodríguez-González,
- Carmen Valenzuela-Silva,
- Belinda Sánchez-Ramírez,
- Laura Rodríguez-Noda,
- Rocmira Pérez-Nicado,
- Raul González-Mugica,
- Tays Hernández-García,
- Talía Fundora-Barrios,
- Martha Dubet Echevarría,
- Juliet María Enriquez-Puertas,
- Yenicet Infante-Hernández,
- Ariel Palenzuela-Díaz,
- Evelyn Gato-Orozco,
- Yanet Chappi-Estévez,
- Julio Cesar Francisco-Pérez,
- Miladi Suarez-Martinez,
- Ismavy C. Castillo-Quintana,
- Sonsire Fernandez-Castillo,
- Yanet Climent-Ruiz,
- Darielys Santana-Mederos,
- Yanelda García-Vega,
- María Eugenia Toledo-Romani,
- Delaram Doroud,
- Alireza Biglari,
- Yury Valdés-Balbín,
- Dagmar García-Rivera,
- Vicente Vérez-Bencomo,
- María Elena Mesa-Herrera,
- Yarmila García-Cristiá,
- Leonor Verdecia-Sánchez,
- Rafael del Valle Rodríguez,
- Yudalvies Oquendo-de la Cruz,
- Daysi Álvarez-Montalvo,
- Randy Grillo-Fortún,
- Liset López-González,
- Omaida Fonte Galindo,
- Yeseni Reyes-González,
- Ana Beatriz González-Álvarez,
- Linet Gorrita-Mora,
- Rodrigo Valera-Fernández,
- Ivis Ontivero-Pino,
- Marisel Martínez-Pérez,
- Esperanza Caballero-Gonzalez,
- Aniurka Garcés-Hechavarría,
- Dayle Martínez-Bedoya,
- Maite Medina-Nápoles,
- Yeney Regla Domínguez-Pentón,
- Yadira Cazañas-Quintana,
- Thais Fundora Barrios,
- Diana R. Hernández Fernández,
- Gretchen Bergado-Báez,
- Ivette Orosa-Vazquez,
- Franciscary Pi-Estopiñan,
- Marianniz Díaz-Hernández,
- Otto Cruz-Sui,
- Enrique Noa-Romero,
- Arilia García-López,
- Sandra Rivadereira Muro,
- Gerardo Baro-Roman
Affiliations
- Rinaldo Puga-Gómez
- Pediatric Hospital “Juan Manuel Marquez,” Havana, Cuba; Central Clinic “Cira García”, La Habana, Cuba
- Yariset Ricardo-Delgado
- Pediatric Hospital “Juan Manuel Marquez,” Havana, Cuba
- Chaumey Rojas-Iriarte
- Policlinic “5 de Septiembre”, La Habana, Cuba
- Leyanis Céspedes-Henriquez
- Policlinic “Carlos J. Finlay”, La Habana, Cuba
- Misleidys Piedra-Bello
- Pediatric Hospital “Juan Manuel Marquez,” Havana, Cuba
- Dania Vega-Mendoza
- Pediatric Hospital “Juan Manuel Marquez,” Havana, Cuba
- Noelvia Pestana Pérez
- Pediatric Hospital “Juan Manuel Marquez,” Havana, Cuba
- Beatriz Paredes-Moreno
- Finlay Vaccine Institute, Havana, Cuba
- Meiby Rodríguez-González
- Finlay Vaccine Institute, Havana, Cuba
- Carmen Valenzuela-Silva
- Cybernetics, Mathematics, and Physics Institute, La Habana, Cuba
- Belinda Sánchez-Ramírez
- Centre of Molecular Immunology, Havana, Cuba
- Laura Rodríguez-Noda
- Finlay Vaccine Institute, Havana, Cuba
- Rocmira Pérez-Nicado
- Finlay Vaccine Institute, Havana, Cuba
- Raul González-Mugica
- Finlay Vaccine Institute, Havana, Cuba
- Tays Hernández-García
- Centre of Molecular Immunology, Havana, Cuba
- Talía Fundora-Barrios
- Centre of Molecular Immunology, Havana, Cuba
- Martha Dubet Echevarría
- National Civil Defense Research Laboratory, Mayabeque, Cuba
- Juliet María Enriquez-Puertas
- National Civil Defense Research Laboratory, Mayabeque, Cuba
- Yenicet Infante-Hernández
- National Civil Defense Research Laboratory, Mayabeque, Cuba
- Ariel Palenzuela-Díaz
- Centre for Immunoassays, La Habana, Cuba
- Evelyn Gato-Orozco
- Centre for Immunoassays, La Habana, Cuba
- Yanet Chappi-Estévez
- National Clinical Trials Coordinating Center, Havana, Cuba
- Julio Cesar Francisco-Pérez
- Pediatric Hospital “Borrás-Marfán”, La Habana, Cuba
- Miladi Suarez-Martinez
- Policlinic “Carlos J. Finlay”, La Habana, Cuba
- Ismavy C. Castillo-Quintana
- Finlay Vaccine Institute, Havana, Cuba
- Sonsire Fernandez-Castillo
- Finlay Vaccine Institute, Havana, Cuba
- Yanet Climent-Ruiz
- Finlay Vaccine Institute, Havana, Cuba
- Darielys Santana-Mederos
- Finlay Vaccine Institute, Havana, Cuba
- Yanelda García-Vega
- Centre of Molecular Immunology, Havana, Cuba
- María Eugenia Toledo-Romani
- “Pedro Kourí” Tropical Medicine Institute, Habana, Cuba
- Delaram Doroud
- Pasteur Institute of Iran, Tehran, Islamic Republic of Iran
- Alireza Biglari
- Pasteur Institute of Iran, Tehran, Islamic Republic of Iran
- Yury Valdés-Balbín
- Finlay Vaccine Institute, Havana, Cuba
- Dagmar García-Rivera
- Finlay Vaccine Institute, Havana, Cuba; Corresponding author.
- Vicente Vérez-Bencomo
- Finlay Vaccine Institute, Havana, Cuba
- María Elena Mesa-Herrera
- Pediatric Hospital “Juan Manuel Marquez,” Havana, Cuba
- Yarmila García-Cristiá
- Pediatric Hospital “Juan Manuel Marquez,” Havana, Cuba
- Leonor Verdecia-Sánchez
- Pediatric Hospital “Juan Manuel Marquez,” Havana, Cuba
- Rafael del Valle Rodríguez
- Pediatric Hospital “Juan Manuel Marquez,” Havana, Cuba
- Yudalvies Oquendo-de la Cruz
- Pediatric Hospital “Juan Manuel Marquez,” Havana, Cuba
- Daysi Álvarez-Montalvo
- Pediatric Hospital “Juan Manuel Marquez,” Havana, Cuba
- Randy Grillo-Fortún
- Pediatric Hospital “Juan Manuel Marquez,” Havana, Cuba
- Liset López-González
- Pediatric Hospital “Juan Manuel Marquez,” Havana, Cuba
- Omaida Fonte Galindo
- Policlinic “Carlos J. Finlay”, La Habana, Cuba
- Yeseni Reyes-González
- Policlinic “Carlos J. Finlay”, La Habana, Cuba
- Ana Beatriz González-Álvarez
- Policlinic “Carlos J. Finlay”, La Habana, Cuba
- Linet Gorrita-Mora
- Policlinic “Carlos J. Finlay”, La Habana, Cuba
- Rodrigo Valera-Fernández
- Finlay Vaccine Institute, Havana, Cuba
- Ivis Ontivero-Pino
- Finlay Vaccine Institute, Havana, Cuba
- Marisel Martínez-Pérez
- Finlay Vaccine Institute, Havana, Cuba
- Esperanza Caballero-Gonzalez
- Finlay Vaccine Institute, Havana, Cuba
- Aniurka Garcés-Hechavarría
- Finlay Vaccine Institute, Havana, Cuba
- Dayle Martínez-Bedoya
- Finlay Vaccine Institute, Havana, Cuba
- Maite Medina-Nápoles
- Finlay Vaccine Institute, Havana, Cuba
- Yeney Regla Domínguez-Pentón
- Finlay Vaccine Institute, Havana, Cuba
- Yadira Cazañas-Quintana
- Centre of Molecular Immunology, Havana, Cuba
- Thais Fundora Barrios
- Centre of Molecular Immunology, Havana, Cuba
- Diana R. Hernández Fernández
- Centre of Molecular Immunology, Havana, Cuba
- Gretchen Bergado-Báez
- Centre of Molecular Immunology, Havana, Cuba
- Ivette Orosa-Vazquez
- Centre of Molecular Immunology, Havana, Cuba
- Franciscary Pi-Estopiñan
- Centre of Molecular Immunology, Havana, Cuba
- Marianniz Díaz-Hernández
- Centre of Molecular Immunology, Havana, Cuba
- Otto Cruz-Sui
- National Civil Defense Research Laboratory, Mayabeque, Cuba
- Enrique Noa-Romero
- National Civil Defense Research Laboratory, Mayabeque, Cuba
- Arilia García-López
- National Clinical Trials Coordinating Center, Havana, Cuba
- Sandra Rivadereira Muro
- National Clinical Trials Coordinating Center, Havana, Cuba
- Gerardo Baro-Roman
- Centre for Immunoassays, La Habana, Cuba
- Journal volume & issue
-
Vol. 126
pp. 164 – 173
Abstract
Objectives: To evaluate a heterologous vaccination scheme in children 3-18 years old (y/o) combining two SARS-CoV-2r- receptor binding domain (RBD)protein vaccines. Methods: A phase I/II open-label, adaptive, and multicenter trial evaluated the safety and immunogenicity of two doses of FINLAY-FR-2 (subsequently called SOBERANA 02) and the third heterologous dose of FINLAY-FR-1A (subsequently called SOBERANA Plus) in 350 children 3-18 y/o in Havana Cuba. Primary outcomes were safety (phase I) and safety/immunogenicity (phase II) measured by anti-RBD immunoglobulin (Ig)G enzyme-linked immunoassay (ELISA), molecular and live-virus neutralization titers, and specific T-cells response. A comparison with adult immunogenicity and predictions of efficacy were made based on immunological results. Results: Local pain was the unique adverse event with frequency >10%, and none was serious neither severe. Two doses of FINLAY-FR-2 elicited a humoral immune response similar to natural infection; the third dose with FINLAY-FR-1A increased the response in all children, similar to that achieved in vaccinated young adults. The geometric mean (GMT) neutralizing titer was 173.8 (95% confidence interval [CI] 131.7; 229.5) vs Alpha, 142 (95% CI 101.3; 198.9) vs Delta, 24.8 (95% CI 16.8; 36.6) vs Beta and 99.2 (95% CI 67.8; 145.4) vs Omicron. Conclusion: The heterologous scheme was safe and immunogenic in children 3-18 y/o. Trial registry: https://rpcec.sld.cu/trials/RPCEC00000374