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Immunogenicity and reactogenicity of BNT162b2 booster in ChAdOx1-S-primed participants (CombiVacS): a multicentre, open-label, randomised, controlled, phase 2 trial

2021; Elsevier BV; Volume: 398; Issue: 10295 Linguagem: Inglês

10.1016/s0140-6736(21)01420-3

1474-547X

Alberto M. Borobia, Antonio J. Carcas, Mayte Pérez‐Olmeda, Luís Castaño, María Jesús Bertrán, Javier García‐Pérez, M. Josefa Campins, Antonio Portolés, María González-Pérez, Maria Teresa García Morales, Eunate Arana‐Arri, Marta Aldea, Francisco Díez‐Fuertes, Inmaculada Fuentes-Durá, Ana Ascaso, David Lora, Natale Imaz-Ayo, Lourdes E. Barón-Mira, Antònia Agustí, Carla Pérez-Ingidua, Agustı́n Gómez de la Cámara, José Ramón Arribas, Jordi Ochando, José Alcamı́, Cristóbal Belda-Iniesta, Jesús Frías, Lucía Martínez de Soto, Amelia Rodríguez Mariblanca, Lucía Díaz García, Elena Ramı́rez, Enrique Seco Meseguer, Stefan Stewart, Alicia Marín Candón, Irene García-García, Mikel Urroz, Jaime Monserrat Villatoro, Paula de la Rosa, Marta Sanz García, Cristina López Crespo, Vega Mauleón Martínez, Raquel de Madariaga Castell, Laura Vitón Vara, Julio García‐Rodríguez, Antonio Buño Soto, Eduardo López Granados, Carmen Cámara, Esther Rey Cuevas, Pilar Ayllon García, María Jiménez-González, Victoria Hernández Rubio, Paloma Moraga Alapont, Amparo Rodríguez Sánchez, Rocío Prieto, Silvia Llorente Gómez, Cristina Miragall Roig, Marina Aparicio Marlasca, Fernando Calle, Marta Arsuaga, B. Duque, Susana Meijide, Aitor García de Vicuña, Ana Santorcuato, Iraide Expósito, Sara Benito, Joseba Andia, Cristina Castillo, Esther Irurzun, Jesús Camino, Mikel Temprano, Josune Goikoetxea, Alazne Bustinza, Maialen Larrea, Mikel Gallego, Dolores García-Vázquez, Ana B. de la Hoz, Gustavo Pérez de Nanclares, Estíbaliz Pérez-Guzmán, Eneko Idoyaga, Adriana Lamela, Jesús Oteo, María Castillo de la Osa, Lourdes Hernández Gutiérrez, María Elena Andrés Galván, Esther Calonge, María Elena Andrés Galván, Mercedes Bermejo, Humberto Erick de la Torre-Tarazona, Almudena Cascajero, Giovanni Fedele, Concepción Perea, Isabel Cervera, Irene Bodega‐Mayor, María Montes‐Casado, Pilàr Portolés, Jana Baranda, Laura Granés, Sulayman Lazaar, Sara Herranz, María Eugènia Mellado, Marta Tortajada, Montserrat Malet, Sebastiana Quesada, Anna Vilella, Anna Llupià, Victòria Olivé, Antoni Trilla, Begoña Gómez, Elisenda González, Sheila Romero, Francisco Javier Gámez, Cristina Casals, Laura Burunat, Juan José Castelló, Patricia Fernández, Josep Lluís Bedini, Jordi Vilà, Carla Aguilar, Carmen Altadill, Lluı́s Armadans, Blanca Borrás-Bermejo, Julia Calonge, Lina Camacho-Arteaga, Anna Feliu‐Prius, Gisela Gili, Cesar Llorente, Xavier Martínez‐Gómez, Susana Otero‐Romero, Esther Palacio, Oleguer Parés‐Badell, Laia Pinós, Aitana Plaza, Judit Riera‐Arnau, José Ángel Rodrigo‐Pendás, Carla Sans-Pola, José Ramón Santos, Gloria Torres, Margarita Torrens, Sonia Uriona, Elena Ballarin Alins, E. Pérez, Lourdes Vendrell Bosch, Leonor Laredo, Diana Uribe López, Esperanza González‐Rojano, Manuel Sánchez-Craviotto, A. Paterna, Teresa Iglesias Hernán-Gómez, Natalia Rodríguez Galán, José Antonio Gil Marín, Verónica Álvarez-Morales, Ana Belén Navalpotro, M Dolores Jiménez-Santamaría, M Carmen Cardós, Elena Hermoso, Mar García-Arenillas, Natalia Pérez Macías, Alexandra Domingo Fernández, Amanda López Picado, Jorge Mario Quiñones, Nicoletta Deidda, Ana García‐Franco, José María Torvisco,

Heparin-Induced Thrombocytopenia and Thrombosis

BackgroundTo date, no immunological data on COVID-19 heterologous vaccination schedules in humans have been reported. We assessed the immunogenicity and reactogenicity of BNT162b2 (Comirnaty, BioNTech, Mainz, Germany) administered as second dose in participants primed with ChAdOx1-S (Vaxzevria, AstraZeneca, Oxford, UK).MethodsWe did a phase 2, open-label, randomised, controlled trial on adults aged 18–60 years, vaccinated with a single dose of ChAdOx1-S 8–12 weeks before screening, and no history of SARS-CoV-2 infection. Participants were randomly assigned (2:1) to receive either BNT162b2 (0·3 mL) via a single intramuscular injection (intervention group) or continue observation (control group). The primary outcome was 14-day immunogenicity, measured by immunoassays for SARS-CoV-2 trimeric spike protein and receptor binding domain (RBD). Antibody functionality was assessed using a pseudovirus neutralisation assay, and cellular immune response using an interferon-γ immunoassay. The safety outcome was 7-day reactogenicity, measured as solicited local and systemic adverse events. The primary analysis included all participants who received at least one dose of BNT162b2 and who had at least one efficacy evaluation after baseline. The safety analysis included all participants who received BNT162b2. This study is registered with EudraCT (2021-001978-37) and ClinicalTrials.gov (NCT04860739), and is ongoing.FindingsBetween April 24 and 30, 2021, 676 individuals were enrolled and randomly assigned to either the intervention group (n=450) or control group (n=226) at five university hospitals in Spain (mean age 44 years [SD 9]; 382 [57%] women and 294 [43%] men). 663 (98%) participants (n=441 intervention, n=222 control) completed the study up to day 14. In the intervention group, geometric mean titres of RBD antibodies increased from 71·46 BAU/mL (95% CI 59·84–85·33) at baseline to 7756·68 BAU/mL (7371·53–8161·96) at day 14 (p<0·0001). IgG against trimeric spike protein increased from 98·40 BAU/mL (95% CI 85·69–112·99) to 3684·87 BAU/mL (3429·87–3958·83). The interventional:control ratio was 77·69 (95% CI 59·57–101·32) for RBD protein and 36·41 (29·31–45·23) for trimeric spike protein IgG. Reactions were mild (n=1210 [68%]) or moderate (n=530 [30%]), with injection site pain (n=395 [88%]), induration (n=159 [35%]), headache (n=199 [44%]), and myalgia (n=194 [43%]) the most commonly reported adverse events. No serious adverse events were reported.InterpretationBNT162b2 given as a second dose in individuals prime vaccinated with ChAdOx1-S induced a robust immune response, with an acceptable and manageable reactogenicity profile.FundingInstituto de Salud Carlos III.TranslationsFor the French and Spanish translations of the abstract see Supplementary Materials section.