Antigenic and Molecular Genetic Evolution of Influenza Viruses in Kazakhstan from 2017 to 2025

Influenza viruses undergo continuous genetic and antigenic evolution, making sustained surveillance essential for monitoring changes in virus circulation and vaccine relevance. We analyzed influenza epidemiology and viral evolution in Kazakhstan across eight consecutive epidemic seasons (2017/18–2024/25) using data from the national influenza sentinel surveillance system, together with antigenic characterization, Sanger sequencing, whole-genome sequencing, and phylogenetic analysis. Influenza activity was almost undetectable during the 2020/21 season, followed by the re-emergence of A(H3N2)-dominated circulation in 2021/22. In 2022/23, influenza B predominated initially, followed by A(H1N1)pdm09, whereas A(H3N2) predominated in 2023/24. A total of 199 A(H1N1)pdm09, 157 A(H3N2), 105 B/Victoria, and 16 B/Yamagata viruses were genetically characterized. A(H1N1)pdm09 viruses showed successive replacement of 6B-derived lineages, with descendants of 6B.1A.5a.2a predominating in the post-pandemic period. A(H3N2) viruses showed substantial genetic diversification, progressing from 3C.2a descendants to 3C.2a1b-related viruses and subsequently to 2a.3a.1/J.2 viruses. Among B/Victoria viruses, V1A was successively replaced by V1A.3 and V1A.3a.2, with V1A.3a.2 accounting for 100% of genetically characterized viruses in 2023/24 and 2024/25. Antigenic analysis showed 16- to 32-fold lower HI titers for A(H1N1)pdm09 6B.1A.5a.2 viruses when tested against antisera to earlier vaccine/reference strains, whereas no detectable antigenic differences were observed between 6B.1A.5a.2a and its recent descendants. These findings demonstrate substantial post-pandemic changes in influenza epidemic timing, subtype dominance, and genetic composition in Kazakhstan, while circulating viruses remained within globally recognized evolutionary lineages. Integrated epidemiological, genetic, and antigenic surveillance is important for detecting emerging variants, assessing vaccine relevance, and supporting timely influenza prevention and control measures.