{"paper_id":"01b044ac-b378-4512-83ff-988e451ea3bc","body_text":"Abstract\nAims COVID-19 disease burden in United States (US) older adults ≥65 years and persons with underlying medical conditions remains high. This modeling study provides an interim estimate of the anticipated public health impact of the next-generation COVID-19 mRNA-1283 vaccine in these populations at high-risk of severe COVID-19 outcomes.\nMethods mRNA-1283 was compared to no vaccination and originally licensed mRNA COVID-19 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 the 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. Clinical outcomes calculated included total numbers of symptomatic infections, outpatient and long COVID cases, hospitalizations, and deaths. Sensitivity and scenario analyses were performed.\nResults During the 2024/2025 season in the US, a single dose of the mRNA-1283 vaccine was estimated to prevent approximately 2.9 (1.3-4.3) million symptomatic infections, 171,000 (77,000-260,000) hospitalizations, and 22,350 (10,050-33,480) deaths compared to no vaccination. Compared to BNT162b2, mRNA-1283 was estimated to avert an additional 0.79 million symptomatic infections, 58,000 hospitalizations, and 7,565 deaths. Compared to mRNA-1273, mRNA-1283 was estimated to avert an additional 0.56 million symptomatic infections, 46,000 hospitalizations, and 5,920 deaths. Across all scenarios the majority of severe COVID-19 cases (i.e., hospitalizations and deaths) were prevented among older adults ≥65 years.\nLimitations The real-world effectiveness and safety of mRNA-1283 have not yet been established and the relative VE estimates should be validated with real-world data. Future COVID-19 incidence and incidence pattern throughout the season is uncertain.\nConclusions Interim results suggest that the next-generation COVID-19 mRNA-1283 vaccine could substantially reduce the clinical burden of COVID-19 among those at high risk of severe disease. Compared to no vaccination and originally approved mRNA vaccines, mRNA-1283 provides a valuable option to potentially enhance COVID-19 immunization programmes and protection of those most vulnerable.\nCompeting Interest Statement\nDeclaration of Funding: This study was supported by Moderna, Inc. Declaration of competing interests: MK is a shareholder in Quadrant Health Economics Inc, which was contracted by Moderna, Inc. to conduct this study. AL, KF, MW and SC are consultants to Quadrant Health Economics Inc. KJ, NV and EB are employed by Moderna, Inc. and may hold stock/stock options in the company.\nFunding Statement\nThis study was supported by Moderna, Inc.\nAuthor Declarations\nI confirm all relevant ethical guidelines have been followed, and any necessary IRB and/or ethics committee approvals have been obtained.\nYes\nI confirm that all necessary patient/participant consent has been obtained and the appropriate institutional forms have been archived, and that any patient/participant/sample identifiers included were not known to anyone (e.g., hospital staff, patients or participants themselves) outside the research group so cannot be used to identify individuals.\nYes\nI understand that all clinical trials and any other prospective interventional studies must be registered with an ICMJE-approved registry, such as ClinicalTrials.gov. I confirm that any such study reported in the manuscript has been registered and the trial registration ID is provided (note: if posting a prospective study registered retrospectively, please provide a statement in the trial ID field explaining why the study was not registered in advance).\nYes\nI have followed all appropriate research reporting guidelines, such as any relevant EQUATOR Network research reporting checklist(s) and other pertinent material, if applicable.\nYes\nData Availability\nAll data produced in the present work are contained in the manuscript.","source_license":"Public-Domain","license_restricted":false}