Decision Analysis Modeling Favors Optimal Influenza Vaccination in Late November or Early December

Background: Waning vaccine protection and variable epidemic timing create a tradeoff between vaccinating before influenza circulation and preserving protection when disease burden is greatest. Existing guidance does not quantify the week that best balances this tradeoff. Objective: To estimate the optimal week for influenza vaccination while accounting for uncertainty in epidemic timing and vaccine protection. Design: Simulation-based probabilistic decision analysis. Setting: United States outpatient influenza surveillance from the 50 states and District of Columbia during the 2010/11 through 2018/19 and 2023/24 through 2025/26 seasons. Participants: People in the United States who would receive 1 influenza vaccine dose. Interventions: Vaccination during Morbidity and Mortality Weekly Report (MMWR) weeks 36 through 12. Measurements: We combined influenza-like illness (ILI) syndromic surveillance and influenza-specific data with uncertainty in epidemic timing, initial vaccine effectiveness, waning, and immune-response lag. For each candidate week, the model estimated direct protection against outpatient surveillance burden. Results: The primary model identified the optimal time to vaccinate as week 47, with weeks 47-48 being of similar utility. Our influenza-weighted outpatient analysis (ILI+) selected week 48. Compared with week 44, near the end of the current September-October guidance window, week 48 reduced modeled influenza-weighted outpatient burden by 50 visit equivalents per 10,000 weekly encounters. Limitations: The model assumed vaccination would occur, used outpatient surveillance burden rather than severe outcomes, and did not incorporate transmission effects. Conclusion: Under the primary waning model, these findings favor vaccinating during weeks 47-48, approximately late November through early December, for most one-dose recipients.