Antigenic variants of influenza B viruses isolated in Japan during the 2017-2018 and 2018-2019 influenza seasons

Background Here, we genetically and antigenically analyzed influenza B viruses (IBVs) isolated in Japan during the 2017-2018 and 2018-2019 influenza seasons. Methods A total of 68 IBVs (61 B/Yamagata/16/88-like [B/Yamagata]-lineage and 7 B/Victoria/2/87-like [B/Victoria]-lineage) were antigenically and genetically characterized by using hemagglutination inhibition (HI) assays and phylogenetic analysis, respectively. The susceptibility of IBVs to neuraminidase (NA) inhibitors was assessed by using a fluorescence-based NA inhibition assay. Results All 61 B/Yamagata-lineage isolates were genetically closely related to B/Phuket/3073/2013, the vaccine strain for these two seasons. Eleven B/Yamagata-lineage isolates tested were antigenically similar to B/Phuket/3073/2013 by the HI test. Seven B/Victoria-lineage isolates were genetically closely related to B/Texas/02/2013, the WHO-recommended vaccine strain for the 2017-2018 season; however, they were antigenically distinct from B/Texas/02/2013 with an eightfold or 16-fold difference in HI titer. Of these 7 isolates, 4 possessed a two-amino-acid deletion at positions 162 and 163 in hemagglutinin (HA) and the other 3 had a three-amino-acid deletion at positions 162-164 in HA. Importantly, the variants with the three-amino-acid deletion appeared to be antigenically different from the B/Colorado/06/2017 virus with the two-amino-acid deletion, the vaccine strain for the 2018-2019 season with a fourfold or eightfold difference in HI titer. One B/Yamagata-lineage isolate carrying a G407S mutation in its NA showed a marked reduction in susceptibility to zanamivir, peramivir, and laninamivir. Conclusions These results highlight the need for continued monitoring for the prevalence of the antigenic variant with the three-amino-acid deletion and the variant with reduced NA inhibitor susceptibility.