The potential benefits of delaying seasonal influenza vaccine selections for the Northern Hemisphere: a retrospective modeling study in the United States

Antigenic similarity between vaccine viruses and circulating viruses is crucial for achieving high vaccine effectiveness against seasonal influenza. New non-egg-based vaccine production technologies could revise current vaccine formulation schedules. We aim to assess the potential benefit of delaying seasonal influenza vaccine virus selection decisions. We identified seasons where season-dominant viruses presented increasing prevalence after vaccine formulation had been decided in February for the Northern Hemisphere, contributing to their antigenic discrepancy with vaccine viruses. Using a SEIR model of seasonal influenza in the United States, we evaluated the impact of updating vaccine decisions with more antigenically-similar vaccine viruses on the influenza burden in the United States. In 2014/15 and 2019/20, the season-dominant A(H3N2) subclade and B/Victoria clade respectively presented increasing prevalence after vaccine decisions were already made for the Northern Hemisphere. Our model showed that the updated A(H3N2) vaccine could have averted 5,000-65,000 influenza hospitalizations in the United States in 2014/15, whereas updating the B/Victoria vaccine component did not substantially change influenza burden in 2019/20 season. With rapid vaccine production, revising current timelines for vaccine selection could result in substantial epidemiological benefits, particularly when additional data could help improve the antigenic match between vaccine and circulating viruses.