Published on March 7, 2018

During the past nearly 50 years, antigenic variants of subtype H3N2 influenza A viruses have frequently emerged, causing significant public health challenges. The manner in which these variants emerge and their patterns of spread are not well understood. We identified 15 antigenic drift events with 16 antigenic variants during 1968–2016 by using a novel genomic sequence–based antigenicity inference method on ~40,000 H3N2 viruses. New antigenic variants were shown to emerge from certain locations in other continents rather than from Asia alone, and variants emerged year-round and took <2 months to spread across multiple continents. The uncertainty of the location of antigenic variant emergence and the rapidity of viral spread pose great challenges for influenza surveillance. Our findings suggest that a more robust H3N2 virus surveillance strategy, including sampling from unrepresented areas (e.g., tropical locations) and outside influenza seasons, would help identify the emergence of antigenic variants.