Antibodies from the 2025-2026 influenza vaccine recognize H3N2 subclade K in many people.

A Public Health Alerts report of 76 people found post-vaccination seropositivity against H3N2 subclade K rose to about 39% (from 11% before vaccination), while seropositivity to the 2025-2026 H3N2 vaccine strain rose to 71%.

A Public Health Alerts report summarizes a study of antibody responses to the 2025-2026 seasonal influenza vaccine. The Public Health Alerts collaboration, produced by NEJM Evidence and CIDRAP, aims to translate frontline observations into expert-reviewed public health evidence. Researchers at the University of Pennsylvania analyzed blood samples taken before vaccination and 27–30 days after a standard dose. The analysis compared responses to the 2025-2026 H3N2 vaccine strain and a widely circulating H3N2 variant called subclade K. Key findings: - The study enrolled 76 participants who received the egg-based 2025-2026 Flulaval Trivalent vaccine (GSK). - Hemagglutination inhibition (HAI) assays were used to measure strain-specific antibody responses before and after vaccination. - Before vaccination, 39% (30 of 76) of participants were seropositive (HAI titer ≥40) to the vaccine H3N2 strain and 11% (8 of 76) were seropositive to H3N2 subclade K. - After vaccination, seropositivity rose to 71% for the vaccine strain and to 39% for subclade K. - Geometric mean antibody titers after vaccination were approximately twofold higher to the vaccine strain than to subclade K, and results did not vary substantially by participant age. - The authors reported that antigenic differences observed in human sera were smaller than previously reported in ferret studies and concluded the vaccine induces antibodies that are, from a regulatory perspective, likely to provide protection against H3N2 subclade K. Summary: The report indicates the 2025-2026 influenza vaccine elicits antibodies that recognize H3N2 subclade K in a notable proportion of recipients, while producing stronger responses to the vaccine strain. The authors note antigenic advancement of subclade K compared with the vaccine strain but that human-serum differences were smaller than ferret data suggested. Undetermined at this time.