Influenza Vaccine Effectiveness and Safety for the 2026-2027 Respiratory Season

Influenza continues to cause significant mortality and morbidity in the US. Seasonal influenza vaccines reduce the severity of disease and prevent hospitalizations and death, especially among individuals at high risk.

To identify and summarize the most recently published research spanning several influenza seasons reporting on the epidemiology of influenza in the US and the effectiveness and safety of US-licensed seasonal influenza vaccines, updating a prior evidence review through August 2025.

This systematic review searched Medline (PubMed), Embase, Cochrane CENTRAL, and Scopus from August 1, 2025, through June 30, 2026, for all English-language studies. Eligible publications reported on the epidemiology of influenza in the US or vaccine effectiveness and safety for any influenza vaccine formulation approved for use in the US. Data extraction included effectiveness and safety estimates reported among older adults; adults; during pregnancy; infants, children, and young adults; and persons who were immunocompromised. Risk of bias assessment was conducted.

The search identified 69 eligible studies: 21 randomized clinical trials (RCTs) and 23 observational studies with a comparator group, 7 product safety studies without a comparator group, and 18 descriptive studies of disease burden. Across multiple seasons, influenza vaccines were associated with reduced risk of influenza-related hospitalization (vaccine effectiveness [VE] ranging from 19.0%; 95% CI, 0.0%-34.0% to 43.0%; 95% CI, 30.0%-53.0%) and mortality (VE ranging from 29.0%; 95% CI, 16.0%-40.0% to 65.8%; 95% CI, 54.6%-76.9%) among older adults. Vaccines were also associated with reduced risk of severe influenza among infants, children, adolescents, and young adults; a case-cohort analysis of national surveillance data over 8 seasons (2016-2020 and 2021-2025) among infants, children, and adolescents aged 6 months to 17 years reported that VE was 80.0% (95% CI, 75.0%-84.0%) against laboratory-confirmed influenza-associated deaths. Vaccination during pregnancy was associated with a VE against symptomatic disease in infants of 44.4% (95% CI, 31.4%-54.9%) based on a retrospective cohort study from 2011 to 2022. RCT data published in 2025 for seasons 2022 to 2025 reported higher efficacy against hospitalization with the high-dose compared with standard-dose vaccine among older adults (relative VE, 43.6%; 95% CI, 27.5%-56.3%). A large self-controlled case series among 9 973 703 individuals receiving vaccines found no association with increased risk of serious adverse events, including Guillain-Barré syndrome, after the seasonal influenza vaccine was administered alone or when coadministered with respiratory syncytial virus or COVID-19 immunizations. Another self-controlled case series reported no association with increased risk of febrile seizure during the interval 0 to 7 days after vaccination.

This systematic review found that evidence published August 1, 2025, through June 30, 2026, continued to demonstrate that influenza vaccines were associated with reduced risk of severe disease and hospitalization, especially among older adults, infants, children, and young adults. No new safety concerns were identified.