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Emerging SARS-COV-2 variants are spurring the development of adapted vaccines as public health authorities plan for fall vaccinations. This study estimated the number of infections and hospitalizations prevented by three potential booster strategies for adults (≥18 years) in the United States: boosting with either Moderna’s (1) licensed first generation monovalent vaccine mRNA-1273 (ancestral strain) or (2) candidate bivalent vaccine mRNA-1273.214 (ancestral + BA.1 variant of concern [VOC]) starting in September 2022, or (3) Moderna’s updated candidate bivalent vaccine mRNA-1273.222 (ancestral + BA.4/5 VOC) starting November 2022 due to longer development time. An age-stratified, transmission dynamic, Susceptible-Exposed-Infection-Recovered (SEIR) model, adapted from previous literature, was used to estimate infections over time; the model contains compartments defined by SEIR and vaccination status. A decision tree was used to estimate clinical consequences of infections. Calibration was performed so the model tracks the actual course of the pandemic to present time. Vaccinating with mRNA-1273(Sept), mRNA-1273.214(Sept), and mRNA-1273.222(Nov) is predicted to reduce infections by 34%, 40%, and 18%, respectively, and hospitalizations by 42%, 48%, and 25%, respectively, over 6 months compared to no booster. Sensitivity analyses around transmissibility, vaccine coverage, masking, and waning illustrate that boosting with mRNA-1273.214 in September prevented more cases of infection and hospitalization than the other vaccines. With the emergence of new variants, key characteristics of the virus that affect estimates of spread and clinical impact also evolve, making parameter estimation difficult. Our analysis demonstrated that boosting with mRNA-1273.214 was more effective over 6 months in preventing infections and hospitalizations with a BA.4/5 subvariant than the tailored vaccine, simply because it could be deployed 2 months earlier. We conclude that there is no advantage to delay boosting until a more effective BA.4/5 vaccine is available; earlier boosting with mRNA-1273.214 will prevent the most infections and hospitalizations.

The potential clinical impact of implementing different COVID-19 boosters in fall 2022 in the United States