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

• Published in: International journal of infectious diseases 2023-01, Vol.126, p.164-173
• Main Authors: Puga-Gómez, Rinaldo, Ricardo-Delgado, Yariset, Rojas-Iriarte, Chaumey, Céspedes-Henriquez, Leyanis, Piedra-Bello, Misleidys, Vega-Mendoza, Dania, Pérez, Noelvia Pestana, Paredes-Moreno, Beatriz, Rodríguez-González, Meiby, Valenzuela-Silva, Carmen, Sánchez-Ramírez, Belinda, Rodríguez-Noda, Laura, Pérez-Nicado, Rocmira, González-Mugica, Raul, Hernández-García, Tays, Fundora-Barrios, Talía, Echevarría, Martha Dubet, Enriquez-Puertas, Juliet María, Infante-Hernández, Yenicet, Palenzuela-Díaz, Ariel, Gato-Orozco, Evelyn, Chappi-Estévez, Yanet, Francisco-Pérez, Julio Cesar, Suarez-Martinez, Miladi, Castillo-Quintana, Ismavy C., Fernandez-Castillo, Sonsire, Climent-Ruiz, Yanet, Santana-Mederos, Darielys, García-Vega, Yanelda, Toledo-Romani, María Eugenia, Doroud, Delaram, Biglari, Alireza, Valdés-Balbín, Yury, García-Rivera, Dagmar, Vérez-Bencomo, Vicente, Mesa-Herrera, María Elena, García-Cristiá, Yarmila, Verdecia-Sánchez, Leonor, del Valle Rodríguez, Rafael, Oquendo-de la Cruz, Yudalvies, Álvarez-Montalvo, Daysi, Grillo-Fortún, Randy, López-González, Liset, Galindo, Omaida Fonte, Reyes-González, Yeseni, González-Álvarez, Ana Beatriz, Gorrita-Mora, Linet, Valera-Fernández, Rodrigo, Ontivero-Pino, Ivis, Martínez-Pérez, Marisel, Caballero-Gonzalez, Esperanza, Garcés-Hechavarría, Aniurka, Martínez-Bedoya, Dayle, Medina-Nápoles, Maite, Domínguez-Pentón, Yeney Regla, Cazañas-Quintana, Yadira, Barrios, Thais Fundora, Fernández, Diana R. Hernández, Bergado-Báez, Gretchen, Orosa-Vazquez, Ivette, Pi-Estopiñan, Franciscary, Díaz-Hernández, Marianniz, Cruz-Sui, Otto, Noa-Romero, Enrique, García-López, Arilia, Muro, Sandra Rivadereira, Baro-Roman, Gerardo
• Format: Article
• Language: English
• Subjects: Adolescent; Antibodies, Neutralizing; Antibodies, Viral; Carrier Proteins; Child; Child, Preschool; Conjugate vaccine; COVID-19; COVID-19 - prevention & control; COVID-19 Vaccines - adverse effects; Heterologous scheme; Humans; Pediatric vaccine; RBD vaccine; SARS-CoV-2; Subunit vaccine; Tetanus Toxoid; Vaccines, Conjugate; Young Adult
• ISSN: 1201-9712; 1878-3511
• DOI: 10.1016/j.ijid.2022.11.016

•FINLAY-FR-2 conjugate vaccine is safe and immunogenic in children 3-18 years old.•The third dose with FINLAY-FR-1A (dimer receptor binding domain vaccine) increases the immune response.•The heterologous three-dose schedule elicited specific T-cell response.•This vaccination elicits neutralizing antibodies vs the Delta and Omicron variants of concern.•Immune response in children is non-inferior to young adults. 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. 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. 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. The heterologous scheme was safe and immunogenic in children 3-18 y/o. https://rpcec.sld.cu/trials/RPCEC00000374