Why Influenza Subclade K Became Dominant—And What It Means for Influenza Vaccine Strategy

Subclade K emerged as a dominant influenza A/H3N2 strain in 2025, accounting for more than 90% of infections globally. Surprisingly, seasonal vaccines elicited measurable cross-reactive antibody responses deemed protective—yet the strain still spread rapidly.

A new study authored by one of EVA therapeutics founders, Dr. Annie De Groot, reveals why: T cell epitope loss. Using EpiCC, a new immunoinformatics tool developed by Annie and colleagues while she was CEO of EpiVax, researchers found a 10% reduction in cross-conserved T cell epitope content between seasonal vaccines, circulating strains, and subclade K.

The implications are striking. Decreased cross-conservation may signal the emergence of new flu strains, and proactive analysis of cross-conserved T cell epitopes may improve vaccine selection.

The bigger picture: Current influenza vaccine strain selection relies almost exclusively on antibody responses measured in ferrets—missing half the immunity story. T cells contribute substantially to protection against infection and severe disease.

This work suggests a paradigm shift: incorporating T cell epitope analysis into global influenza strain selection could improve vaccine effectiveness and help predict future variant dominance—not just for flu, but for any rapidly mutating respiratory virus.

Read the full article here at Taylor & Francis Online.