Immunogenicity and reactogenicity of BNT162b2 booster in ChAdOx1-S-primed participants (CombiVacS): a multicentre, open-label, randomised, controlled, phase 2 trial. Issue 10295 (10th July 2021)

• Record Type: Journal Article
• Authors: Borobia, Alberto M; Carcas, Antonio J; Pérez-Olmeda, Mayte; Castaño, Luis; Bertran, María Jesús; García-Pérez, Javier; Campins, Magdalena; Portolés, Antonio; González-Pérez, María; García Morales, María Teresa; Arana-Arri, Eunate; Aldea, Marta; Díez-Fuertes, Francisco; Fuentes, Inmaculada; Ascaso, Ana; Lora, David; Imaz-Ayo, Natale; Barón-Mira, Lourdes E; Agustí, Antonia; Pérez-Ingidua, Carla; Gómez de la Cámara, Agustín; Arribas, José Ramón; Ochando, Jordi; Alcamí, José; Belda-Iniesta, Cristóbal; Frías, Jesús; Martínez de Soto, Lucía; Rodríguez Mariblanca, Amelia; Díaz García, Lucía; Ramírez García, Elena; Seco Meseguer, Enrique; Stewart Balbás, Stefan Mark; Marín Candón, Alicia; García García, Irene; Urroz Elizalde, Mikel; Monserrat Villatoro, Jaime; de la Rosa, Paula; Sanz García, Marta; López Crespo, Cristina; Mauleón Martínez, Vega; de Madariaga Castell, Raquel; Vitón Vara, Laura; García Rodríguez, Julio; Buño, Antonio; López Granados, Eduardo; Cámara, Carmen; Rey Cuevas, Esther; Ayllon García, Pilar; Jiménez González, María; Hernández Rubio, Victoria; Moraga Alapont, Paloma; Sánchez, Amparo; Prieto, Rocío; Llorente Gómez, Silvia; Miragall Roig, Cristina; Aparicio Marlasca, Marina; de la Calle, Fernando; Arsuaga, Marta; Duque, Blanca; Meijide, Susana; García de Vicuña, Aitor; Santorcuato, Ana; Expósito, Iraide; de Benito, Sara; Andia, Joseba; Castillo, Cristina; Irurzun, Esther; Camino, Jesús; Temprano, Mikel; Goikoetxea, Josune; Bustinza, Alazne; Larrea, Maialen; Gallego, Mikel; García-Vázquez, Dolores; de la Hoz, Ana Belén; Pérez-Nanclares, Gustavo; Pérez-Guzmán, Estíbaliz; Idoyaga, Eneko; Lamela, Adriana; Oteo, Jesús; Castillo de la Osa, María; Hernández Gutiérrez, Lourdes; Andrés Galván, María Elena; Calonge, Esther; Andrés Galván, María Elena; Bermejo, Mercedes; de la Torre-Tarazona, Erick Humberto; Cascajero, Almudena; Fedele, Giovanni; Perea, Concepción; Cervera, Isabel; Bodega-Mayor, Irene; Montes-Casado, María; Portolés, Pilar; Baranda, Jana; Granés, Laura; Lazaar, Sulayman; Herranz, Sara; Mellado, María Eugènia; Tortajada, Marta; Malet, Montserrat; Quesada, Sebastiana; Vilella, Anna; Llupià, Anna; Olivé, Victoria; Trilla, Antoni; Gómez, Begoña; González, Elisenda; Romero, Sheila; Gámez, Francisco Javier; Casals, Cristina; Burunat, Laura; Castelló, Juan José; Fernández, Patricia; Bedini, Josep Lluís; Vila, Jordi; Aguilar, Carla; Altadill, Carmen; Armadans, Lluis; Borras-Bermejo, Blanca; Calonge, Julia; Camacho, Lina; Feliu, Anna; Gili, Gisela; Llorente, Cesar; Martínez-Gómez, Xavier; Otero-Romero, Susana; Palacio, Esther; Parés, Oleguer; Pinós, Laia; Plaza, Aitana; Riera-Arnau, Judit; Rodrigo-Pendás, José Angel; Sans, Carla; Santos, José; Torres, Gloria; Torrens, Margarita; Uriona, Sonia; Ballarin Alins, Elena; Pérez Esquirol, Eulàlia; Vendrell Bosch, Lourdes; Laredo Velasco, Leonor; Uribe López, Diana; González Rojano, Esperanza; Sánchez-Craviotto, Manuel; Rivas Paterna, Ana Belén; Hernán-Gómez, Teresa Iglesias; Rodríguez Galán, Natalia; Gil Marín, José Antonio; Álvarez-Morales, Verónica; Navalpotro, Ana Belén; Jiménez-Santamaría, M Dolores; Cardós, M Carmen; Hermoso, Elena; García-Arenillas, Mar; Pérez Macías, Natalia; Domingo Fernández, Alexandra; López Picado, Amanda; Quiñones, Jorge Mario; Deidda, Nicoletta; García-Franco, Ana; Torvisco, José María;
• Is Part Of: Lancet. Volume 398:Issue 10295(2021)
• Page Start: 121
• Page End: 130
• Publication Date: 2021-07-10
• Subjects: Medicine -- Periodicals; Medicine -- Periodicals; Medicine; Medicine; Electronic journals; Periodicals; 610.5
• DOI: 10.1016/S0140-6736(21)01420-3
• Languages: English
• ISSNs: 0140-6736

Abstract

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-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. 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<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. 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.