Genetic variation and vaccine match of influenza B virus in Riyadh, Saudi Arabia during three consecutive seasons, 2020-2023.

In Saudi Arabia, where millions from different countries converge on the holy sites of Makkah and Madina, surveillance of respiratory viruses, especially influenza viruses, is of utmost importance. The influenza B virus (IBV) is constantly changing genetically, which affects vaccine effectiveness and immune evasion. While IBV epidemiology has been studied extensively around the world, little is known about its genetic dynamics in Saudi Arabia. The current study aims to investigate the genetic evolution, antigenic diversity, and potential vaccine mismatches of IBV in Riyadh throughout the 2020-2023 epidemic season. IBV-positive samples underwent whole-HA and NA gene sequencing and phylogenetic analysis. The HA and NA genes were examined for mutations, antigenic site amino acid substitutions, and glycosylation patterns. Divergence was assessed using a comparative examination of vaccination strains. During the three study seasons (winters 2020/21, 2021/22, and 2022/23), 5.26% of participants had confirmed IBV profiles, mostly female children aged 5-12 years. The HA gene contains 118 mutations, 46 of which are amino acid substitutions with significant antigenic site changes. In comparison to the B/Austria/1359417/2021 vaccination strain, 50 mutations were found, including a unique 9-nucleotide deletion. Increased O-glycosylation in Riyadh isolates indicates improved immune evasion. The phylogenetic analysis reveals that all Riyadh isolates (n = 20) belong to the B/Victoria lineage. The major lineage, B/Victoria V1A.3a.2, is consistent with worldwide circulation patterns. IBV in Riyadh shows high genetic drift and antigenic diversity, which may limit vaccine effectiveness. Continuous genomic surveillance is critical for detecting new mutations and directing vaccination updates.