Strain Matching of Seasonal Influenza Vaccines and Emergence of Neuraminidase Inhibitor Resistance in China from 2015 to 2025

Background: Influenza remains a major global public health threat, and vaccination is one of the most effective preventive measures. However, frequent antigenic drift and occasional antigenic shift, along with the lead time required for vaccine development and regional differences in the evolution of circulating strains, may lead to mismatches between WHO-recommended vaccine strains and circulating viruses. In addition, antiviral resistance further complicates precise influenza prevention and control. Objectives: This study aimed to evaluate the concordance of vaccine strains with circulating influenza viruses and the emergence of neuraminidase inhibitor (NAI) resistance in China. Methods: Data on antigenic characterization and antiviral susceptibility testing were extracted from weekly influenza surveillance reports published by the Chinese National Influenza Center from 2015 to 2025. Viral evolution, substitutions at key antigenic sites, and resistance-associated mutations were further examined based on sequences of circulating influenza viruses in China. Results: The overall vaccine match rates were 95.72% (95% CI: 94.02–97.43%) for A(H1N1)pdm09, 58.96% (95% CI: 54.93–62.96%) for A(H3N2), 64.45% (95% CI: 59.49–69.41%) for B/Victoria, and 95.19% (95% CI: 91.32–99.05%) for B/Yamagata in China during the 2015–2025 influenza seasons, with marked year-to-year fluctuations observed particularly for A(H3N2) and B/Victoria. The vaccine matching for cell-based A(H3N2) (70.41%, 95% CI: 65.04–75.77%) vaccine reference strains was significantly higher than that for egg-based A(H3N2) (48.09%, 95% CI: 42.63–53.55%) vaccine reference strains. Sequence analysis indicated that circulating A(H3N2) viruses showed the greatest genetic divergence from the matched egg-based vaccine strains (2.71%, 95% CI: 2.66–2.75%). Phenotypic NAI resistance was detected only in A(H1N1)pdm09 viruses, with resistance rates of 0.18% (95% CI: 0.07–0.45%) in 2023, 3.47% (95% CI: 2.63–4.57%) in 2024, and 3.01% (95% CI: 2.46–3.68%) in 2025. Neuraminidase (NA) sequence analysis showed that the key NAI resistance-associated substitution H274Y has been detected in A(H1N1)pdm09 viruses since 2015, at relatively high frequencies observed during 2015–2018. The mutation re-emerged in 2023 and presented increase trends thereafter, although no A(H1N1) pdm09 circulated during the COVID-19 pandemic. Conclusions: Antigenic concordance between vaccine strains and circulating A(H3N2) or B/Victoria viruses showed marked year-to-year fluctuations in China. Cell-based A(H3N2) vaccine reference strains showed higher antigenic concordance than egg-based strains, supporting further consideration of vaccine production platforms in A(H3N2)-predominant seasons. Phenotypic NAI resistance in circulating A(H1N1)pdm09 viruses was detected from 2023 onward in China, whereas resistance-associated NA substitutions had been detected earlier at the sequence level.