BNT162b2 Versus mRNA-1273 Vaccines: Comparative Analysis of Long-Term Protection Against SARS-CoV-2 Infection and Severe COVID-19 in Qatar

Abstract

Background: This study provides a head-to-head comparison of the protection provided by the BNT162b2 and mRNA-1273 vaccines against SARS-CoV-2 infection and against severe COVID-19, covering primary series and third dose/booster vaccinations over up to 3 years of follow-up, both before and after the emergence of the omicron variant. Methods: Two national, matched, retrospective cohort studies were conducted on Qatar's vaccinated population from December 16, 2020, to February 18, 2024. Subgroup analyses by pre-vaccination SARS-CoV-2 infection history, as well as sensitivity analyses, were also conducted. Results: The adjusted hazard ratio (AHR) comparing infection incidence in those vaccinated with BNT162b2 versus mRNA-1273 was 1.03 (95% CI: 1.02–1.05) after the primary series and 1.11 (95% CI: 1.09–1.13) after the third (booster) dose. The corresponding AHRs for any severe, critical, or fatal COVID-19 were 1.31 (95% CI: 0.81–2.11) and 1.00 (95% CI: 0.20–4.94), respectively. Subgroup analyses by prior infection status hinted at a dose-dependent immune imprinting effect, where a combination of two types of immunity, pre-omicron and omicron, offered greater protection against infection than one type alone, with this effect being amplified by the higher antigen dose of mRNA-1273 compared to BNT162b2. Sensitivity analyses confirmed the study findings. Conclusions: BNT162b2 provided slightly less protection against infection than mRNA-1273 following both primary series and booster vaccinations while offering comparable protection against severe COVID-19 outcomes. The findings suggested that the vaccine antigen dose in interaction with infection history may determine the extent of immune protection against infection.