Reduced Influenza B-specific Post-Vaccination Antibody Cross-reactivity in the B/Victoria Lineage Predominant 2019/20 Season.

Background The influenza activity of the 2019/20 season remained high and widespread in the US with type B viruses predominating the early season. The majority of B viruses characterized belonged to B/Victoria (B/Vic) lineage and contained a triple deletion of amino acid (aa) 162-164 in hemagglutinin (3DEL). These 3DEL viruses are antigenically distinct from B/Colorado/06/2017 (CO/06) - the B/Vic vaccine component of the 2018/19 and 2019/20 seasons representing the viruses with a double deletion of aa 162-163 in hemagglutinin (2DEL). Methods We performed molecular characterization and phylogenetic analysis of circulating B/Vic viruses. We also conducted hemagglutination inhibition (HAI) assay using archived human post-vaccination sera collected from healthy subjects administered with different types of 2018/19 or 2019/20 seasonal vaccines. Their HAI cross-reactivity to representative 3DEL viruses were analyzed. Results The CO/06-specific human post-vaccination sera, after being adjusted for vaccine type, had significantly reduced HAI cross-reactivity toward representative 3DEL viruses, especially the 136E+150K subgroup. The geometric mean titers against 3DEL viruses containing 136E+150K mutations were 1.6-fold lower in all population (p=0.051) and 1.9-fold lower in adults (p=0.016) as compared to those against the 136E+150N viruses. Conclusions Our results indicate that post-vaccination antibodies induced by the B/Vic vaccine component of the 2019/20 influenza season had reduced HAI cross-reactivity toward predominant 3DEL viruses in the US. A close monitoring of 3DEL 136E+150K subgroup is warranted should this subgroup return and predominate the 2020/21 influenza season.