Substitutions near the HA receptor binding site explain the origin and major antigenic change of the B/Victoria and B/Yamagata lineages

Significance Influenza viruses are estimated to infect up to 20% of people during annual epidemics, causing substantial morbidity and mortality, particularly among risk groups. Vaccines continue to be the best available preventive measure, but their efficacy is hindered by constant viral immune evasion. Two cocirculating influenza B virus lineages, B/Victoria and B/Yamagata, are antigenically distinct, and immunity against one lineage does not protect optimally against infection with the other. By investigating the genetic and antigenic data of a historical influenza B virus collection, we reconstructed the antigenic evolution and identified the molecular determinants of the early antigenic diversification. This research improves our understanding of the emergence of new antigenic variants of influenza virus, important for influenza vaccine design and strain selection.

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