Indirect comparison of the relative vaccine effectiveness of mRNA-1283 vs. BNT162b2 vaccines against symptomatic COVID-19 among US adults.

Abstract

Background: COVID-19 continues to pose a significant health burden, particularly among older adults. mRNA-1283 is a next-generation COVID-19 mRNA vaccine developed to enhance immune response. Findings from the Phase 3 NextCOVE trial comparing bivalent versions of mRNA-1273 and mRNA-1283 vaccines have recently become available. However, there are no head-to-head trials comparing mRNA-1283 and the BNT162b2 vaccine.

Objective: To indirectly compare the effectiveness of mRNA-1283 and BNT162b2 against symptomatic COVID-19 among adults in the U.S.

Methods: A targeted literature review was conducted to identify relevant studies comparing the mRNA-1273 and BNT162b2 bivalent vaccines. A real-world evidence (RWE) study by Kopel et al. (2023) assessing the relative vaccine effectiveness (rVE) of mRNA-1273 vs. BNT162b2, was selected for an indirect treatment comparison (ITC) against the NextCOVE trial using the Bucher method. Analyses were stratified by age group, and sensitivity analyses were conducted using alternative outcome definitions.

Results: Despite differences between NextCOVE and the Kopel study, comparability assessments supported a robust ITC. Among participants ≥18 years of age, the indirect rVE of mRNA-1283 vs. BNT162b2 against symptomatic COVID-19 was 15.3% (95% CI: 4.7-24.8%, p = 0.006). For adults ≥65 years of age, the rVE was 22.8% (95% CI: 3.7-38.1%, p = 0.022). Sensitivity analyses with alternative outcome definitions supported these estimates.

Conclusion: This analysis provides consistent and statistically significant evidence indicating the next-generation mRNA-1283 vaccine is more effective in preventing symptomatic COVID-19 than BNT162b2, with the largest effect in individuals aged ≥65. Consistent results across sensitivity analyses underscore the robustness of the findings, offering important evidence to inform vaccination decisions by policymakers, providers, and payers.