In response to low-moderate seasonal vaccination efficacy, rapid genetic changes in circulating viruses, and long vaccine manufacturing turnaround times, broadly protective, long-lasting universal influenza vaccines are being developed. Because a long-lasting vaccination may be less effective than a seasonal vaccine tailored to currently circulating strains, the public health impact of its introduction should be assessed. A modified agent-based model (ABM) was used to investigate the long-term consequences of a universal vaccination administered in Year 1 solely to those aged 18 to 49. The parameters for the model were derived from US databases and the medical literature. The outcomes were cumulative and annual influenza cases during a 4-year period, as well as yearly cases averted/100,000 population for three age groups: 0–17 years, 18–49 years, and 50+ years. More influenza cases occurred in Year 1 when universal vaccination was provided to 50% or 100% of all immunized 18–49-year-olds, compared to no universal vaccine, but fewer instances occurred in Years 2–4 as overall protection improved. Cumulative avoided instances in 18 to 49-year-olds over 4 years were 892/100,000 and 1,687/100,000 for the 50 percent and 100 percent universal vaccination scenarios, respectively, with additional benefits to children and older individuals through indirect effects.

In ABM, the universal vaccination with a conservative VE estimate was administered once to 18–49-year-olds and decreased influenza cases in all age groups. If the VE of universal vaccinations surpasses the value estimated in these models, the influenza load may be reduced sooner.