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Background Vaccination is the best way to prevent influenza; however, greater benefits could be achieved. To help guide research and policy agendas, we aimed to quantify the magnitude of influenza disease that would be prevented through targeted increases in vaccine effectiveness (VE) or vaccine coverage (VC). Methods For 3 influenza seasons (2011–12, 2015–16, and 2017–18), we used a mathematical model to estimate the number of prevented influenza-associated illnesses, medically attended illnesses, and hospitalizations across 5 age groups. Compared with estimates of prevented illness during each season, given observed VE and VC, we explored the number of additional outcomes that would have been prevented from a 5% absolute increase in VE or VC or from achieving 60% VE or 70% VC. Results During the 2017–18 season, compared with the burden already prevented by influenza vaccination, a 5% absolute VE increase would have prevented an additional 1 050 000 illnesses and 25 000 hospitalizations (76% among those aged ≥65 years), while achieving 60% VE would have prevented an additional 190 000 hospitalizations. A 5% VC increase would have resulted in 785 000 fewer illnesses (56% among those aged 18–64 years) and 11 000 fewer hospitalizations; reaching 70% would have prevented an additional 39 000 hospitalizations. Conclusions Small, attainable improvements in effectiveness or VC of the influenza vaccine could lead to substantial additional reductions in the influenza burden in the United States. Improvements in VE would have the greatest impact in reducing hospitalizations in adults aged ≥65 years, and VC improvements would have the largest benefit in reducing illnesses in adults aged 18–49 years.

Projected Population Benefit of Increased Effectiveness and Coverage of Influenza Vaccination on Influenza Burden in the United States