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

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From: The Lancet(Vol. 398, Issue 10295)
Publisher: Elsevier B.V.
Document Type: Report
Length: 1,136 words

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Summary Background To 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). Methods We 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-[gamma] 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. Findings Between 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 Interpretation BNT162b2 given as a second dose in individuals prime vaccinated with ChAdOx1-S induced a robust immune response, with an acceptable and manageable reactogenicity profile. Funding Instituto de Salud Carlos III. Translations For the French and Spanish translations of the abstract see Supplementary Materials section. Author Affiliation: (a) Servicio de Farmacología Clínica, Departamento de Farmacología y Terapéutica, Facultad de Medicina, Hospital Universitario La Paz, IdiPAZ, Universidad Autónoma de Madrid, Madrid, Spain (b) Servicio de Medicina Interna, Hospital Universitario La Paz, IdiPAZ, Universidad Autónoma de Madrid, Madrid, Spain (c) Laboratorio de Serología, Instituto de Salud Carlos III, Madrid, Spain (d) Unidad de Inmunopatología del SIDA, Instituto de Salud Carlos III, Madrid, Spain (e) Laboratorio de Referencia en Inmunología, Instituto de Salud Carlos III, Madrid, Spain (f) Centro Nacional de Microbiología, and Evaluation and Promotion of Research, Instituto de Salud Carlos III, Madrid, Spain (g) Hospital Universitario de Cruces, Biocruces Bizkaia HRI, UPV/EHU, OSAKIDETZA, CIBERDEM, CIBERER, Endo-ERN, Barakaldo-Bilbao, Spain (h) Servicio de Medicina Preventiva y Epidemiología, Hospital Clínic de Barcelona, Barcelona, Spain (i) Servicio de Medicina Preventiva y Epidemiología, Servicio de Farmacología Clínica, Hospital Universitari Vall d'Hebron, Universitat Autònoma de Barcelona, Barcelona, Spain (j) Unidad de Soporte a la Investigación Clínica, Vall d'Hebron Institut de Recerca, Servicio de Farmacología Clínica, Hospital Universitari Vall d'Hebron, Universitat Autònoma de Barcelona, Barcelona, Spain (k) Departmento de Farmacología, Terapéutica y Toxicología, Servicio de Farmacología Clínica, Hospital Universitari Vall d'Hebron, Universitat Autònoma de Barcelona, Barcelona, Spain (l) Servicio de Farmacología Clínica, Hospital Clínico San Carlos, IdISSC, Departamento de Farmacología y Toxicología, Universidad Complutense de Madrid, Madrid, Spain (m) Instituto de Investigación Sanitaria Hospital 12 de Octubre, CIBER de Epidemiología y Salud Pública, Facultad de Medicina, Universidad Complutense de Madrid, Madrid, Spain * Correspondence to: Dr Cristóbal Belda-Iniesta, Evaluation and Promotion of Research, Instituto de Salud Carlos III, Madrid 28029, Spain (footnote)* Contributed equally (footnote)[Dagger] Contributed equally (footnote)[double dagger] Study group members are listed in appendix 3 Byline: Alberto M Borobia, PhD (a), Prof Antonio J Carcas, PhD (a), Mayte Pérez-Olmeda, PhD (c), Prof Luis Castaño, PhD (g), María Jesús Bertran, PhD (h), Javier García-Pérez, PhD (d), Prof Magdalena Campins, PhD (i), Prof Antonio Portolés, PhD (l), María González-Pérez, MSc (e), María Teresa García Morales, MSc (m), Eunate Arana-Arri, PhD (g), Marta Aldea, MD (h), Francisco Díez-Fuertes, PhD (d), Inmaculada Fuentes, PhD (j), Ana Ascaso, MD (l), David Lora, PhD (m), Natale Imaz-Ayo, PharmG (g), Lourdes E Barón-Mira, MD (h), Antonia Agustí, PhD (k), Carla Pérez-Ingidua, BSN (l), Agustín Gómez de la Cámara, PhD (m), José Ramón Arribas, PhD (b), Jordi Ochando, PhD (e), José Alcamí, PhD (d), Cristóbal Belda-Iniesta, PhD [cbelda@isciii.es] (f,[Dagger]), Prof Jesús Frías, PhD [jesus.frias@uam.es] (a,**,[Dagger]), Lucía Martínez de Soto, Amelia Rodríguez Mariblanca, Lucía Díaz García, Elena Ramírez García, Enrique Seco Meseguer, Stefan Mark Stewart Balbás, Alicia Marín Candón, Irene García García, Mikel Urroz Elizalde, 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, Eduardo López Granados, Carmen Cámara, Esther Rey Cuevas, Pilar Ayllon García, María Jiménez González, Victoria Hernández Rubio, Paloma Moraga Alapont, Amparo Sánchez, Rocío Prieto, Silvia Llorente Gómez, Cristina Miragall Roig, Marina Aparicio Marlasca, Fernando de la Calle, Marta Arsuaga, Blanca Duque, Susana Meijide, Aitor García de Vicuña, Ana Santorcuato, Iraide Expósito, Sara de Benito, Joseba Andia, Cristina Castillo, Esther Irurzun, Jesús Camino, Mikel Temprano, Josune Goikoetxea, Alazne Bustinza, Maialen Larrea, Mikel Gallego, Dolores García-Vázquez, Ana Belén de la Hoz, Gustavo Pérez-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, Erick Humberto de la Torre-Tarazona, Almudena Cascajero, Giovanni Fedele, Concepción Perea, Isabel Cervera, Irene Bodega-Mayor, María Montes-Casado, Pilar Portolés, Jana Baranda, Laura Granés, Sulayman Lazaar, Sara Herranz, María Eugènia Mellado, Marta Tortajada, Montserrat Malet, Sebastiana Quesada, Anna Vilella, Anna Llupià, Victoria 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 Vila, Carla Aguilar, Carmen Altadill, Lluis Armadans, Blanca Borras-Bermejo, Julia Calonge, Lina Camacho, Anna Feliu, Gisela Gili, Cesar Llorente, Xavier Martínez-Gómez, Susana Otero-Romero, Esther Palacio, Oleguer Parés, Laia Pinós, Aitana Plaza, Judit Riera-Arnau, José Angel Rodrigo-Pendás, Carla Sans, José Santos, Gloria Torres, Margarita Torrens, Sonia Uriona, Elena Ballarin Alins, Eulàlia Pérez Esquirol, Lourdes Vendrell Bosch, Leonor Laredo Velasco, Diana Uribe López, Esperanza González Rojano, Manuel Sánchez-Craviotto, Ana Belén Rivas 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

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Gale Document Number: GALE|A667906693