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

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. 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. 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. 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. Most influenza vaccines are produced in hens’ eggs. When vaccine viruses are grown in eggs, mutations may occur that promote better growth in eggs but reduce the effectiveness of the vaccine against circulating human influenza viruses. We compared the effectiveness of egg-based influenza vaccines (QIVe; egg-based quadrivalent influenza vaccine) with QIVc (cell-based quadrivalent influenza vaccine), made by growing vaccine virus in cell lines from mammals. We measured the relative vaccine effectiveness (rVE) of these vaccines in preventing influenza illness. The rVE describes the additional protective benefit provided by one vaccine relative to another. We found that QIVc was significantly more effective in preventing influenza infection among people aged 6 months to 64 years during the 2023–2024 influenza season in the United States: the rVE was +19.8%. Therefore, of the people who would remain unprotected after vaccination with QIVe, vaccination with QIVc would have additionally protected 19.8% of this remaining population. Similar results are seen when we specifically look at either children, adults, or those with health problems that increase the risk of serious influenza complications (rVE ranging from +14.7% to +24.3%). We estimated that if all those aged 6 months to 64 years who were vaccinated during the 2023–2024 US influenza season had received QIVc instead of QIVe, an additional 2.4 million symptomatic influenza illnesses would have been prevented, along with 1.1 million outpatient visits, 14,940 hospitalizations, and 574 deaths. Our data support the benefit of QIVc over QIVe in people aged 6 months to 64 years.