Influenza Vaccines Continue to Reduce Severe Disease and Death Across High-Risk Groups, Evidence Review Finds

An independent systematic review published in JAMA found that influenza vaccination continued to be associated with a reduced risk of severe influenza, influenza-related hospitalization, and influenza-related death across multiple seasons, particularly among older adults, infants, children, and young adults. The review identified no new safety concerns with the vaccines.¹

The Vaccine Integrity Project at the University of Minnesota’s Center for Infectious Disease Research and Policy conducted the review in collaboration with the American Medical Association to inform recommendations for the 2026-2027 respiratory season.²

The CDC estimates that the 2025-2026 season produced around 15 million to 25 million medical visits, 390,000 to 800,000 hospitalizations, and at least 24,000 deaths from influenza. Yet, fewer than half of eligible adults and children received a 2025-2026 influenza vaccine.¹

Immunization remains “one of our best tools for preventing severe illness from respiratory viruses,” Michael T. Osterholm, PhD, MPH, executive director of the Vaccine Integrity Project, said in a news release.²

Review Scope and Methods

Investigators searched 4 databases for English-language studies published between August 1, 2025, and June 30, 2026, updating a prior review conducted through August 2025. Of 5826 records screened, 69 studies were included: 21 randomized clinical trials (RCTs), 23 observational studies with a comparator group, 7 product safety studies without a comparator group, and 18 descriptive studies of disease burden.¹

Protection Among Adults

In the 2025-2026 season, VISION Network data linked vaccination to lower risk of influenza-related hospitalization. Vaccine effectiveness (VE) was 31.0% (95% CI, 21.0%-39.0%) among adults aged 65 years and older and 29.0% (95% CI, 11.0%-45.0%) among adults aged 18 to 64 years. For the 2024-2025 season, VE against influenza-related mortality among older adults ranged from 29.0% (95% CI, 16.0%-40.0%) to 65.8% (95% CI, 54.6%-76.9%).¹

Vaccine formulation also mattered. The DANFLU-2 pragmatic trial (NCT05517174) enrolled more than 332,000 older adults in Denmark. Over 3 seasons, high-dose quadrivalent inactivated vaccine was associated with a relative VE of 43.6% (95% CI, 27.5%-56.3%) against influenza-related hospitalization compared with standard-dose vaccine.¹

Protection Among Children and Infants

Among children and adolescents aged 6 months to 17 years, VE against influenza-related hospitalization ranged from 28.0% in 2021-2022 to 67.0% (95% CI, 56.0%-75.0%) in 2023-2024.¹

National surveillance data spanning 8 seasons showed that vaccination was associated with a VE of 80.0% (95% CI, 75.0%-84.0%) against influenza-associated pediatric deaths. Among children with high-risk medical conditions, VE against death was 77.0% (95% CI, 71.0%-82.0%). Most pediatric deaths occurred among unvaccinated children.¹

Vaccination during any trimester of pregnancy was associated with a VE of 44.4% (95% CI, 31.4%-54.9%) against laboratory-confirmed influenza among infants during their first 6 months of life.¹

Safety Findings and a New mRNA Option

A self-controlled case series included nearly 10 million commercially insured individuals. It found no significantly increased risk of Guillain-Barré syndrome, anaphylaxis, or stroke after standard-dose vaccination. Among children aged 6 months to 5 years, vaccination was not associated with increased risk of febrile seizure. Vaccination during pregnancy was not associated with increased risk of preterm birth. Coadministration with COVID-19 or respiratory syncytial virus vaccines also raised no safety concerns.¹

The review also included data on mRNA-1010 (mFLUSIVA; Moderna), which was licensed in the US in August 2026. In an RCT of 40,703 adults aged 50 years and older, mRNA-1010 had a relative VE of approximately 26.6% (95% CI, 16.7%-35.4%) against laboratory-confirmed influenza-like illness compared with standard-dose vaccine. Grade 3 solicited reactions were more common with mRNA-1010 (6.4% vs 1.0%). Rates of vaccine-related serious adverse events were similar (0.02% vs 0.01%).¹

Recommendations Shift to Medical Societies

Before 2025, the Advisory Committee on Immunization Practices (ACIP) routinely reviewed vaccine data to guide recommendations. That process was disrupted when the US Department of Health and Human Services dismissed ACIP’s members, and an expert-led committee has not been restored.²

The evidence review instead informed 2026-2027 recommendations from 4 societies^2,3:

• The American Academy of Family Physicians recommends an updated influenza vaccine for everyone aged 6 months to 64 years, and an mRNA, adjuvanted, high-dose, or recombinant vaccine for adults 65 years and older.
• The American Academy of Pediatrics recommends annual vaccination for everyone older than 6 months.
• The Infectious Diseases Society of America recommends a high-dose, adjuvanted, inactivated, or recombinant vaccine for immunocompromised patients and advises against live attenuated vaccine in this group.
• The American College of Obstetricians and Gynecologists recommends inactivated or recombinant vaccine during pregnancy and postpartum.

REFERENCES

1. Senerth E, Sheikholeslamian SM, Sivakumaran K, et al. Influenza vaccine effectiveness and safety for the 2026-2027 respiratory season. JAMA. Published online September 2, 2026. doi:10.1001/jama.2026.18126

2. Vaccine Integrity Project and AMA announce completed independent evidence review of respiratory virus immunizations. News release. Vaccine Integrity Project, University of Minnesota. September 2, 2026. Accessed September 24, 2026. https://vaxintegrity.cidrap.umn.edu/2026-27-respiratory-season-evidence-review

3. Holohan M. Vaccine Integrity Project, American Medical Association review COVID, flu, and RSV vaccines. CIDRAP. September 2, 2026. Accessed September 24, 2026. https://www.cidrap.umn.edu/vaccine-integrity-project/vaccine-integrity-project-american-medical-association-review-covid-flu