Can a Two-Dose Influenza Vaccine Regimen Better Protect Older Adults? An Agent-Based Modeling Study

Older adults (age ≥ 65) are at high risk of influenza morbidity and mortality. This study evaluated the impact of a hypothetical two-dose influenza vaccine regimen per season to reduce symptomatic flu cases by providing preseason (first dose) and mid-season (second dose) protection to offset waning vaccine effectiveness (VE). The Framework for Reconstructing Epidemiological Dynamics (FRED), an agent-based modeling platform, was used to compare typical one-dose vaccination to a two-dose vaccination strategy. Primary models incorporated waning VE of 10% per month and varied influenza season timing (December through March) to estimate cases and hospitalizations in older adults. Additional scenarios modeled reductions in uptake and VE of the second dose, and overall waning. In seasons with later peaks, two vaccine doses had the largest potential to reduce cases (14.4% with February peak, 18.7% with March peak) and hospitalizations (13.1% with February peak, 16.8% with March peak). Reductions in cases and hospitalizations still resulted but decreased when 30% of individuals failed to receive a second dose, second dose VE was reduced, or overall waning was reduced to 7% per month. Agent-based modeling indicates that two influenza vaccine doses could decrease cases and hospitalizations in older individuals. The highest impact occurred in the more frequently observed late-peak seasons. The beneficial impact of the two-dose regimen persisted despite model scenarios of reduced uptake of the second dose, decreased VE of the second dose, or overall VE waning.