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Understanding Influenza B virus infections is of critical importance in our efforts to control severe influenza and influenza-related diseases. Until 2020, two genetic lineages of influenza B virus-Yamagata and Victoria-circulated in the population. These lineages are antigenically distinct, but the differences in virus replication or the induction of host cell responses after infection have not been carefully studied. Recent IBV clinical isolates of both lineages were obtained from influenza surveillance efforts of the Johns Hopkins Center of Excellence in Influenza Research and Response and characterized in vitro. B/Victoria and B/Yamagata clinical isolates were recognized less efficiently by serum from influenza-vaccinated individuals in comparison to the vaccine strains. B/Victoria lineages formed smaller plaques on MDCK cells compared to B/Yamagata, but infectious virus production in primary human nasal epithelial cell (hNEC) cultures showed no differences. While ciliated epithelial cells were the dominant cell type infected by both lineages, B/Victoria lineages had a slight preference for MUC5AC-positive cells, and B/Yamagata lineages infected more basal cells. Finally, while both lineages induced a strong interferon response 48 h after infection of hNEC cultures, the B/Victoria lineages showed a much stronger induction of interferon-related signaling pathways compared to B/Yamagata. This demonstrates that the two influenza B virus lineages differ not only in their antigenic structure but also in their ability to induce host innate immune responses.

Influenza B Viruses (IBV) have caused an increasing number of cases over the last 15 years. The focus of this study was to assess the role of egg adapted mutants in IBV vaccines on the reactivity of serum from vaccinated or IBV infected individuals. We focused on the 2017-2018 IBV season as this was a significant influenza year with reported low vaccine effectiveness by the CDC. Patient samples were obtained from Johns Hopkins Adult Emergency Room for virus isolation and antigenic characterization. Antigenic characterization was evaluated using neutralizing antibody assays. Viral characterization was carried out using viral genome sequencing and structural modeling, MDCKSIAT1 growth curves, MDCK Plaque assays and human primary nasal epithelial cell (hNEC) growth curves. In our analysis, we found that in the vaccine strains of both IBV lineages, there was an amino acid change at position 197 (B/Brisbane HA Numbering) that leads to a loss of glycosylation. Our antigenic evaluation shows that there is a significant difference in neutralizing antibody titers between the egg adapted vaccine for the B/Yamagata lineage compared to representative clinical isolates from that season and the cell cultured vaccine. We propose that this loss of a glycosylation site is an important site for propagation in the allantois and that this common site change may play a role in antigenic recognition and therefore immune protection from circulating viruses. Screening egg cultured vaccine viruses for egg adapted mutants, further transitioning vaccine production to mammalian culture models (MDCK) or investigating new models of influenza vaccination may be necessary to improve efficacy of the seasonal influenza vaccine for protection from IBV. [ABSTRACT FROM AUTHOR]