This analysis estimates the economic and clinical impact of a Moderna updated COVID-19 mRNA Fall 2023 vaccine for adults at least 18 years in Japan. A previously developed Susceptible Exposed Infected Recovered (SEIR) model with a 1 year analytic time horizon (September 2023 to August 2024) and consequences decision tree were used to estimate symptomatic infections, COVID19 related hospitalizations, deaths, quality adjusted life years (QALYs), costs, and incremental cost-effectiveness ratio (ICER) for a Moderna updated Fall 2023 vaccine versus no additional vaccination, and versus a Pfizer-BioNTech updated mRNA Fall 2023 vaccine. The Moderna vaccine is predicted to prevent 7.2 million symptomatic infections, 272,100 hospitalizations and 25,600 COVID-19 related deaths versus no vaccine. In the base case (healthcare perspective), the ICER was 1,300,000 Yen/QALY gained ($9,400 USD/QALY gained). Sensitivity analyses suggest results are most affected by COVID 19 incidence, initial vaccine effectiveness (VE), and VE waning against infection. Assuming the relative VE between both bivalent vaccines apply to updated Fall 2023 vaccines, the base case suggests the Moderna version will prevent an additional 1,100,000 symptomatic infections, 27,100 hospitalizations, and 2,600 deaths compared to the Pfizer-BioNTech vaccine. The updated Moderna vaccine is expected to be highly cost effective at a 5 million Yen willingness to pay threshold across a wide range of scenarios.

MK is a shareholder in Quadrant Health Economics Inc, which was contracted by Moderna, Inc. to conduct this study. KF, AL and MM are consultants at Quadrant Health Economics Inc. EB, YH, KJ, and NV are employed by Moderna, Inc. and hold stock/stock options in the company. AI has received honorarium or research consultation fees from Moderna Inc., Pfizer Inc., Takeda Pharmaceuticals Inc., Shionogi Co, Ltd, and AstraZeneca Japan Inc.

This study was supported by Moderna, Inc.

I confirm all relevant ethical guidelines have been followed, and any necessary IRB and/or ethics committee approvals have been obtained.

Yes

I confirm that all necessary patient/participant consent has been obtained and the appropriate institutional forms have been archived, and that any patient/participant/sample identifiers included were not known to anyone (e.g., hospital staff, patients or participants themselves) outside the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.

Yes

I 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).

Yes

I have followed all appropriate research reporting guidelines, such as any relevant EQUATOR Network research reporting checklist(s) and other pertinent material, if applicable.

Yes

All data produced in the present work are contained in the manuscript