Mixed vaccination with ChAdOx1-S followed by BNT162b2 induces a robust humoral immune response [Classics Series]

This study summary is an excerpt from the book 2 Minute Medicine’s The Classics in Medicine: Summaries of the Landmark Trials

1. Levels of antibodies against the trimeric spike protein and receptor-binding domain were 36- and 77-fold higher in the BNT162b2 group compared to control.

2. There were no vaccine-related serious adverse events.

Original Date of Publication: June 2021

Study Rundown: Current research on COVID-19 vaccination has revolved around a homologous dosing schedule (administering the same vaccine sequentially). With supplies becoming scarce globally, the need to interchange COVID-19 vaccines is growing. Until now, limited research has been conducted to assess the effect of a heterologous COVID-19 vaccine schedule in humans. This open-label randomized controlled trial aimed to assess the safety and efficacy of a second dose of BNT162b2 (Pfizer-BioNTech mRNA vaccine) in patients who received a first dose of ChAdOx1-S (AstraZeneca vaccine) approximately 8-12 weeks prior to study enrollment. The primary outcome for this study was immunogenicity to SARS-CoV-2 trimeric spike protein and receptor binding domain (RBD), measured by immunoassay at 14 days after second vaccination. Secondary outcomes included neutralizing antibody titers as measured by neutralization assay at two weeks. According to study results, IgG titers against the spike protein and RBD antibodies both increased from baseline to day 14 in the BNT162b2 booster group. There were no serious vaccine-related adverse events. This study was strengthened by a randomized trial that sampled a large group of individuals from multiple hospitals in Spain.

Click to read the study in the Lancet

In-Depth [randomized control trial]: From April 24 to 30, 2021, 678 patients were assessed for eligibility across five university hospitals in Spain. Included patients were ≥18 years of age who previously received the ChAdOx1-S COVID-19 vaccine 8-12 weeks before screening. Altogether, 676 patients were enrolled and randomized, of which 673 completed the study to day 14 – 448 were assigned to BNT162b2, 441 were included in the immunogenicity analysis vs 448 in reactogenicity analysis, and 226 assigned to control with 222 included in immunogenicity analysis. Mean age among enrolled patients was 44 years (SD 9) and the majority (n = 382, 57%) were women.

Borobia AM, Carcas AJ, Pérez-Olmeda M, Castaño L, Bertran MJ, García-Pérez J, et al. Immunogenicity and reactogenicity of BNT162b2 booster in ChAdOx1-S-primed participants (CombiVacS): a multicentre, open-label, randomised, controlled, phase 2 trial. The Lancet. 2021 Jul;398(10295):121–30.

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