BNT162b2 versus mRNA‐1273 vaccines: comparative analysis of long‐term protection against SARS‐CoV‐2 infection and severe COVID‐19 in Qatar

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.