Influenza vaccine effectiveness against medically attended outpatient illness, United States, 2023-24 season.

Background: The 2023-24 U.S. influenza season was characterized by a predominance of A(H1N1)pdm09 virus circulation with co-circulation 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 2023-24 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 (RT-PCR). 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 sub-type/lineage and A(H1N1)pdm09 genetic subclades.
Results: Among 6,589 enrolled patients, 1,770 (27%) tested positive for influenza including 796 A(H1N1)pdm09, 563 B/Victoria, and 323 A(H3N2). Vaccine effectiveness against any influenza illness was 41% (95% Confidence Interval [CI]: 32 to 49): 28% (95% CI: 13 to 40) against influenza A(H1N1)pdm09, 68% (95% CI: 59 to 76) against B/Victoria, and 30% (95% CI: 9 to 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 41% and provided protection overall against circulating influenza A and B viruses. Serologic studies would help inform differences observed by age groups.
Competing Interests: The US Flu VE Network is funded through a US Centers for Disease Control and Prevention Cooperative Agreement (1U01 IP001180-01, 1U01 IP001181-01, 1U01 IP001182-01, 1U01 IP001184-01, 1U01 IP001189-01, 1U01 IP001191-01, 1U01 IP001193-01, and 1U01 IP001194-01). The University of Pittsburgh site was also supported by National Institutes of Health grant UL1TR001857. EAS has received grants from Protein Sciences Corporation and consulting fees from Johnson and Johnson. EBW has received research funding from Pfizer, Moderna, Seqirus, Najit Technologies, and Clinetic for the conduct of clinical research studies. He has also received support as an advisor to Vaxcyte and Pfizer consultant to ILiAD Biotechnologies, and DSMB member for Shionogi. ETM has received grants from Merck. RKZ has received grants from Sanofi Pasteur. SLH has received grants from Seegene Inc., Abbott, Healgen, Roche, CorDx, Hologic, Cepheid, Janssen, and Wondfo Biotech. All other authors report nothing to disclose.