Abstract
<jats:p>Pandemic influenza poses a constant threat to domestic and global public health with the potential of high morbidity and mortality. Pandemic virus-matched vaccines, though potentially highly efficacious, require a lead time before they can be mass-produced and distributed to the population. For this reason, mitigation strategies that provide protection ahead of widespread viral transmission are highly desirable. Here, we model the impact of a broadly cross-reactive seasonal influenza vaccine on pandemic influenza spread in the U.S. Our findings indicate that as the cross-protective efficacy of the seasonal vaccine against the pandemic variant increases, total hospitalizations are concomitantly reduced. For example, we find that even at typical seasonal vaccine uptake and modest vaccine efficacies against infection and hospitalization with the pandemic variant, total hospitalizations can be decreased by 30% or more across the scenarios considered. In addition, the hospitalization risk for recipients is at least 35% lower than the risk experienced by unvaccinated persons. These results demonstrate that a broadly protective influenza vaccine could serve as a critical component of pandemic preparedness strategies.</jats:p>