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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

Authors
Alberto Borobia,Antonio Carcas
Mayte Pérez‐Olmeda,Luís Castaño,M.J. Bertran,Javier García‐Pérez,M. Campins,Antonio Portolés,María González-Pérez,Maria Morales,Eunate Arana‐Arri,Marta Aldea,Francisco Díez‐Fuertes,Inmaculada Fuentes,Ana Ascaso,David Lora,Natale Imaz-Ayo,Lourdes Barón-Mira,Antònia Agustí,Carla Pérez-Ingidua,Agustı́n Cámara,José Arribas,Jordi Ochando,José Alcamı́,Cristobal Belda‐Iniesta,Jesús Frías,Lucía Soto,Amelia Mariblanca,Lucía García,Elena Ramı́rez,Enrique Meseguer,Stefan Stewart,Alicia Candón,Irene García-García,Mikel Urroz,Carlos Toro,Paula Rosa,Marta García,Cristina Crespo,Vega Martínez,Raquel Castell,Laura Vara,Julio García‐Rodríguez,Antonio Soto,Eduardo Granados,Carmen Cámara,Esther Cuevas,Pilar García,María Jiménez-González,Victoria Rubio,Paloma Alapont,Amparo Sánchez,Rocío Prieto,Silvia Gómez,Cristina Roig,Marina Marlasca,Fernando Calle,Marta Arsuaga,B. Duque,Susana Meijide,Aitor 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 Hoz,Gustavo Nanclares,Estíbaliz Pérez-Guzmán,Eneko Idoyaga,Adriana Lamela,Jesús Oteo,María Osa,Lourdes Gutiérrez,María Galván,Esther Calonge,Mercedes Bermejo,Humberto 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 Mellado,Marta Tortajada,Montserrat Malet,Sebastiana Quesada,Anna Vilella,Anna Llupià,Victòria Olivé,Antoni Trilla,Begoña Gómez,Elisenda González,Sheila Romero,Francisco Gámez,Cristina Casals,Laura Burunat,Juan Castelló,Patricia Fernández,J.L. Bedini,Jordi Vilà,Carla Aguilar,Carmen Altadill,Lluı́s Armadans,Blanca Borràs-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 Rodrigo‐Pendás,Carla Sans-Pola,José Santos,Gloria Torres,Margarita Torrens,Sonia Uriona,Elena Alins,E. Pérez,Lourdes Bosch,Leonor Laredo,Diana López,Esperanza González‐Rojano,Manuel Sánchez-Craviotto,A. Paterna,Teresa Hernán-Gómez,Natalia Galán,José Marín,Verónica Álvarez-Morales,Ana Navalpotro,M Jiménez-Santamaría,M Cardós,Elena Hermoso,Mar García-Arenillas,Natalia Macías,Alexandra Fernández,Amanda Picado,Jorge Quiñones,Nicoletta Deidda,Ana García‐Franco,José Torvisco,María Bertrán,Eunate Arana-Arri,Agustín Cámara,José Gatell
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,Cristóbal Belda-Iniesta
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Published
Jun 25, 2021
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Abstract

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).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-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.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<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.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.Instituto de Salud Carlos III.For the French and Spanish translations of the abstract see Supplementary Materials section.

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