Abstract
BACKGROUND: The 2023-2024 US influenza season was characterized by a predominance of A(H1N1)pdm09 virus circulation with cocirculation of A(H3N2) and B/Victoria viruses. We estimated vaccine effectiveness (VE) in the United States against mild-to-moderate medically attended influenza illness in the 2023-2024 season. METHODS: We enrolled outpatients aged ≥8 months with acute respiratory illness in 7 states. Respiratory specimens were tested for influenza type/subtype by reverse-transcriptase polymerase chain reaction. Influenza VE was estimated with a test-negative design comparing odds of testing positive for influenza among vaccinated versus unvaccinated participants. We estimated VE by virus subtype/lineage and A(H1N1)pdm09 genetic subclades. RESULTS: Among 6629 enrolled patients, 1780 (27%) tested positive for influenza, including 806 with A(H1N1)pdm09, 567 with B/Victoria, and 328 with A(H3N2). VE against any influenza illness was 44% (95% confidence interval, 36%-51%): 29% (15%-41%) against influenza A(H1N1)pdm09, 74% (65%-81%) against B/Victoria, and 30% (8%-47%) against A(H3N2). Statistically significant protection against any influenza was found for all age groups except adults aged 50-64 years. Lack of protection in this age group was specific to influenza A-associated illness. We observed differences in VE by birth cohort and A(H1N1)pdm09 virus genetic subclade. CONCLUSIONS: Vaccination reduced outpatient medically attended influenza overall by 44% and provided protection overall against circulating influenza A and B viruses. Serologic studies would help inform differences observed by age groups.