Antigenic Divergence from the Seasonal Vaccine of the Influenza Virus Strains Circulating in Romania During Three Successive Seasons (2021–2024)

Influenza viruses continue to be an important public health threat. Vaccination is the most effective measure to control the influenza virus circulation. However, these viruses are continuously evolving through antigenic drift/shift, and thus the vaccine efficiency is affected. The aim of this study was to characterize the viral strains circulating in Romania, in a population with declining vaccination coverage, during the last three cold seasons by evaluating the hemagglutinin antigenic relatedness to the vaccine strains. All the available sequences collected between August 2021 and June 2024 were analyzed by using phylogenetic analysis and the P_epitope model to predict vaccine efficacy. The results showed that the 2021/2022 influenza season was dominated by the circulation of highly diverse clades of A(H3N2) viruses with high mutational divergence as compared to the vaccine strain, which might contribute to the reduction in vaccine efficacy. During the 2022/2023 influenza season, both influenza A and B viruses were reported, with few antigenic site mutations. The 2023/2024 influenza season was dominated by the circulation of influenza A viruses: A/H1N1pdm09 clade 6B.1A.5a.2a and A/H3N2 clade 2a.3a.1. The clade 2a.3a.1 also showed high variability when compared to the vaccine strain, presumably leading to reduced vaccine efficacy. This study illustrates the high diversity of influenza viruses circulating in a population with low vaccination coverage during the previous cold seasons. The viral diversity impacted vaccine efficacy, hence the need for public health programs to increase vaccine uptake and improve vaccine formulation in order to limit viral transmission.