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AMB, AJC, JO, and JF are members of the VACCELERATE (European Corona Vaccine Trial Accelerator Platform) Network, which aims to facilitate and accelerate the design and implementation of COVID-19 phase 2 and 3 vaccine trials. JO is a member of the INsTRuCT (Innovative Training in Myeloid Regulatory Cell Therapy) Consortium, a network of European scientists from academia and industry focused on developing innovative immunotherapies. This work is funded by Instituto de Salud Carlos III, a Spanish public body assigned to the Ministry of Science and Innovation that manages and promotes public clinical research related to public health. The Spanish Clinical Trials Platform is a public network funded by the Instituto de Salud Carlos III (grant numbers PTC20/00018 and PT17/0017), the State Plan for Research, Development, and Innovation 2013-16, the State Plan for Scientific and Technical Research and Innovation 2017-20, and the Subdirectorate General for Evaluation and Promotion of Research, Instituto de Salud Carlos III, cofinanced with FEDER funds. CombiVacS was designed under the umbrella of the VACCELERATE project. VACCELERATE and INsTRuCT received funding from the EU's Horizon 2020 Research and Innovation Programme (grant agreement numbers 101037867 and 860003). The Health Institute Carlos III is the Spanish partner in the VACCELERATE project. The authors thank all trial participants, the international data safety monitoring board, and the trial steering committee (appendix 3 pp 26-27). The authors thank Esther Prieto for editorial assistance and writing support (employed by Hospital Universitario La Paz; funded by the Instituto de Salud Carlos III, grant number PCT20/00018). All contributors thank Raquel Yotti for her thorough, critical review of the manuscript, and her contributions to the overall conceptualisation of the clinical trial.

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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

Publicated to:Lancet. 398 (10295): 121-130 - 2021-07-08 398(10295), DOI: 10.1016/S0140-6736(21)01420-3

Authors: Borobia, Alberto M; Carcas, Antonio J; Perez-Olmeda, Mayte; Castano, Luis; Jesus Bertran, Maria; Garcia-Perez, Javier; Campins, Magdalena; Portoles, Antonio; Gonzalez-Perez, Maria; Garcia Morales, Maria Teresa; Arana-Arri, Eunate; Aldea, Marta; Diez-Fuertes, Francisco; Fuentes, Inmaculada; Ascaso, Ana; Lora, David; Imaz-Ayo, Natale; Baron-Mira, Lourdes E; Agusti, Antonia; Perez-Ingidua, Carla; Gomez de la Camara, Agustin; Ramon Arribas, Jose; Ochando, Jordi; Alcami, Jose; Belda-Iniesta, Cristobal; Frias, Jesus

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Abstract

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

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