Mid-season influenza virus genetic characterizations in U.S. Department of War populations, 2025-2026.

Continuous monitoring of influenza antigenic drift is vital for vaccine strain selection. This study utilized global Department of War (DOW) surveillance data to evaluate circulating influenza strains and inform the 2026-2027 Northern Hemisphere influenza vaccine recommendations by the World Health Organization. From September 2025 through February 2026, the Department of Defense Global Respiratory Pathogen Surveillance Program collected and analyzed respiratory specimens from over 100 sentinel sites globally. Influenza-positive samples underwent next-generation sequencing, phylogenetic analysis, and antigenic characterization. Analysis of 1,300 sequences revealed A(H3N2) as the predominant (80.1%) subtype, followed by A(H1N1)pdm09 (10.6%) and B/Victoria (9.3%), with variations between combatant commands. Significant antigenic drift led to the dominance of subclades K, D.3.1/D.3.1.1, and C.3.1, respectively. Testing indicated that the 2025-2026 vaccine components offered reduced protection against these emerging strains. Antigenic cartography confirms that the 2026-2027 vaccine strains provide significantly improved protection against circulating viruses. Antiviral resistance markers for neuraminidase inhibitors such as oseltamivir remain rare, with only 2 identified in A(H1N1)pdm09. These data are critical for maintaining force health protection and assessing vaccine performance within highly mobile DOW populations. Analysis of 2025-2026 influenza season data revealed the predominance of subclades A(H1N1)pdm09 D.3.1/D.3.1.1, A(H3N2) K, and B/Victoria C.3.1. Antigenic cartography employing recent candidate vaccine viruses from the U.S. Centers for Disease Control and Prevention confirmed that the World Health Organization's strain recommendations for the 2026-2027 Northern Hemisphere influenza vaccine provide the best protection against these circulating strains.