Modeling the cost-effectiveness of the next-generation COVID-19 mRNA-1283 vaccine in the United States

COVID-19 disease burden in United States (US) adults ≥65 years and persons with underlying medical conditions remains high. This modeling study estimated the cost-effectiveness of the next-generation COVID-19 mRNA-1283 vaccine in persons aged 12–64 at high risk of severe COVID-19 outcomes and all adults ≥65 years. mRNA-1283 was compared with no annual vaccination and originally licensed mRNA vaccines mRNA-1273 and BNT162b2. Analyses were conducted using a static decision-analytic model (1-year horizon). Vaccine effectiveness (VE) against infection and hospitalization for mRNA-1283 versus no vaccination was based on relative VE (rVE) from the Phase 3 pivotal randomized controlled trial comparing mRNA-1283 against mRNA-1273, and mRNA-1273 real-world data. rVE estimates for mRNA-1283 versus BNT162b2 were based on an indirect treatment comparison. The societal incremental cost per quality-adjusted life-year (QALY) gained and the benefit-cost ratio (BCR) were calculated. During the 2025/2026 season, a single dose of mRNA-1283 was estimated to yield an incremental cost per QALY gained of $16,247 compared with no vaccine. The BCR for the base case strategy ranged from $2.16–9.74 returned for every $1 spent for mRNA-1283. mRNA-1283 was estimated to dominate originally-licensed mRNA-COVID-19 vaccines in analyses of the target population. Results were sensitive to COVID-19 incidence, hospitalization rates, post-discharge mortality rates, and VE. The real-world effectiveness and safety of mRNA-1283 have not yet been established, and relative VE estimates should be validated with real-world data. Full year 2025/2026 COVID-19 incidence and vaccine uptake in the US is uncertain. Study results suggest mRNA-1283 may represent a highly cost-effective strategy (considering a $100,000–150,000 per QALY willingness-to-pay threshold) to reduce COVID-19 burden. Based on rVE assumptions made, mRNA-1283 was estimated to dominate originally-licensed mRNA vaccines in this recommended population. mRNA-1283 may provide a valuable option to optimize US COVID-19 immunization programs and protect those most vulnerable.