Objective To analyze the antigenic variation and genetic characteristics of influenza A(H1N1)pdm09 viruses in Xinjiang Uygur Autonomous Region（Xinjiang） from 2022 to 2025, and understand the variation patterns of subtype.

Methods Influenza A(H1N1)pdm09 virus isolates collected and submitted by the regional influenza surveillance network laboratories were selected for antigenic analysis and genetic sequencing. HA gene sequences were compared for homology and characterized using bioinformatics software MEGA X, BioEdit, ChiPot, and ESPript 3.0.

Results  Surveillance data indicated that influenza A(H1N1)pdm09 viruses exhibited a dynamic pattern of circulation with one-year intervals. Antigenic analysis showed that the majority of local epidemic strains were similar to the vaccine strains. Compared with the WHO-recommended vaccine strains A/Victoria/2570/2019 (for the 2022−2023 influenza surveillance season) and A/Victoria/4897/2022 (for the 2023−2025 influenza surveillance seasons), the nucleotide homology was 97.9%–98.8% and 98.0%–99.7%, respectively, and the amino acid homology was 97.3%–98.5% and 97.8%–100%, respectively. Phylogenetic analysis revealed that the A(H1N1)pdm09 influenza viruses displayed clear temporal evolutionary characteristics, predominantly belonging to clade 6B.1A.5a.2 and its two derived subclades. The majority of strains (86.67%) clustered within the 6B.1A.5a.2a subclade, while a minority (13.33%) belonged to the more derived 6B.1A.5a.2a.1 subclade, together with the vaccine strain A/Victoria/4897/2022. Multiple amino acid variation sites were identified in the primary structure of the HA protein, most of which were located in non-critical regions. Key sites for the 2022−2023 surveillance season were distributed in antigenic determinant regions Ca2, Sb, and the receptor-binding site 220-loop, whereas key sites for the 2024−2025 surveillance season were mainly concentrated in antigenic determinant regions Ca2 and Sa. Conclusion From 2022 to 2025, the influenza A(H1N1)pdm09 virus strains isolated in Xinjiang showed high consistency with the corresponding annual vaccine strains in terms of antigenic properties, homology analysis, and phylogenetic tree construction, supporting the protective efficacy of the current influenza vaccine composition. However, the presence of multiple amino acid variations in the HA protein sequence underscores the need for continuous monitoring of the evolution of the HA gene in this subtype to provide a scientific basis for local influenza prevention and control, vaccine strain selection, and clinical treatment.