Superior Effectiveness and Estimated Public Health Impact of Cell- Versus Egg-Based Influenza Vaccines in Children and Adults During the US 2023-2024 Season.

Introduction: The aim of this study was to assess the relative vaccine effectiveness (rVE) of cell-based versus egg-based quadrivalent influenza vaccines (QIVc versus QIVe) in preventing test-confirmed influenza during the 2023-2024 US influenza season.

Methods: rVE was estimated using a test-negative design applied to a large, linked, real-world dataset. QIVc or QIVe recipients aged 6 months-64 years who were tested for influenza within ± 7 days of an acute respiratory or febrile illness were included. rVE was estimated using doubly robust logistic regression. Analyses were performed for the full, pediatric, adult, outpatient and high-risk populations and by influenza type. Public health impact was assessed using a compartmental influenza burden averted model.

Results: The analysis included 2119 QIVc-cases, 14,750 QIVc-controls, 14,559 QIVe-cases, and 75,351 QIVe-controls. QIVc was superior to QIVe in preventing test-confirmed influenza with an rVE of 19.8% (95% CI 15.7-23.8%) in the full population, and with rVEs of 19.6% (13.6-25.3%) in the pediatric population aged 6 months-17 years and 18.5% (12.1-24.5%) in adults aged 18-64 years. Consistent results were observed for all sensitivity and subgroup analyses against any influenza. If all vaccinated individuals aged 6 months-64 years in the US received QIVc over QIVe, an estimated 2,379,395 additional symptomatic illnesses would have been prevented, with proportionate reductions in related complications.

Conclusions: Our analysis showed superior effectiveness of QIVc over QIVe in preventing test-confirmed influenza among persons aged 6 months-64 years, and provided the first demonstration of superiority in pediatric populations from 6 months of age. A Graphical Abstract is availible for this article.