Assessment of Influenza Trends and Projected Vaccine Efficacy for the 2025-2026 Season

By
Eduardo Azziz-Baumgartner
Alicia Budd
Justin S. Lee
A. Danielle Iuliano
Sascha R. Ellington
Min Z. Levine
Xiao-yu Zheng
Larisa Gubareva
Katherine Adams
Jennifer DeCuir
Catherine H. Bozio
Carrie Reed
Marie K. Kirby
Benjamin Rambo-Martin
Jefferson M. Jones
Matthew Biggerstaff
Shikha Garg
Charles Todd Davis
Tom T. Shimabukuro
Erin Burns
Rebecca Kondor
Sonja J. Olsen
Vivien G. Dugan
VISION Coauthors
Stephanie A. Irving
Allison L. Naleway
Kristin Dascomb
Tamara Sheffield
Malini B. DeSilva
Sara Y. Tartof
Lina S. Sy
Nicola P. Klein
Ousseny Zerbo
Shaun J. Grannis
Brian E. Dixon
Melissa S. Stockwell
Ashley B. Stephens
Toan C. Ong
Michelle A. Barron
Sarah W. Ball
Zachary A. Weber
Emily L. Reeves
Caitlin S. Ray
June 17, 2026

Jama Network Open

Overview

The CDC identified 10 mutations in the hemagglutinin protein of influenza A(H3N2) viruses, including changes at residues K2N, T135K(CHO−), S144N(CHO+), N145S, N158D, I160K, Q173R, K189R, T328A, and S378N. These mutations raised concerns about vaccine-induced antibody evasion. The emergence of subclade K viruses has led to significant influenza activity in the Northern Hemisphere, prompting a review of vaccine effectiveness and public health responses.

Background

Influenza viruses continuously evolve, impacting vaccine effectiveness and public health strategies. The 2025-2026 influenza season has seen an early onset and increased severity, particularly due to the emergence of antigenically drifted A(H3N2) viruses. Understanding these trends is crucial for healthcare professionals to manage influenza outbreaks and vaccination strategies effectively.

Data Highlights

During the 2025-2026 influenza season, the CDC reported a notable increase in influenza-like illness (ILI) visits, with rates exceeding the historical average for this time of year. Laboratory-confirmed cases of influenza A(H3N2) have shown a significant rise, particularly among older adults and children. Vaccine effectiveness studies indicated a reduction in hospitalization rates among vaccinated individuals compared to unvaccinated populations.

Key Findings

The CDC identified 10 mutations in the hemagglutinin protein of influenza A(H3N2) viruses.
These mutations raised concerns about the potential for vaccine-induced antibody evasion.
Subclade K viruses displaced other influenza viruses and caused a protracted epidemic in Australia.
Antigenic characterization indicated evidence of antigenic drift compared to the vaccine reference virus.
Surveillance data from the CDC indicated significant influenza activity in the Northern Hemisphere.

Clinical Implications

Healthcare professionals should be aware of the evolving nature of influenza viruses. Continuous monitoring and assessment of influenza trends are essential.

Conclusion

The emergence of antigenically drifted influenza A(H3N2) viruses necessitates ongoing surveillance and evaluation of vaccine efficacy.

Related Resources & Content

JAMA Network Open, 2024-2025 — Influenza Vaccine and Associated Infection and Death in California
JAMA Network Open, 2017-2023 — Influenza Vaccination Trends Among Children and Adolescents
International Journal of Infectious Diseases, 2025-26 — Influenza vaccine effectiveness in school outbreaks during a A(H3N2) subclade K (J.2.4.1)-dominated season in Beijing, China
MMWR, 2025–26 Influenza Season — Prevention and Control of Seasonal Influenza with Vaccines: Recommendations of the Advisory Committee on Immunization Practices
CDC, 2025–2026 Flu Season Overview
MMWR, Interim Estimates of 2025–26 Seasonal Influenza Vaccine Effectiveness
The Journal of Infectious Diseases — Annual Estimation of Seasonal Influenza Burden in 6 South American Countries: A Retrospective Analysis of SARInet Surveillance Data to Inform Policies
Prevention and Control of Seasonal Influenza with Vaccines: Recommendations of the Advisory Committee on Immunization Practices — United States, 2025–26 Influenza Season | MMWR
2025–2026 Flu Season | Influenza (Flu) | CDC
Interim Estimates of 2025–26 Seasonal Influenza Vaccine Effectiveness — United States, September 2025–February 2026 | MMWR

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