Integrating genotypes and phenotypes improves long-term forecasts of seasonal influenza A/H3N2 evolutionMore about Open Access at the Crick
Authors listJohn Huddleston John R Barnes Thomas Rowe Xiyan Xu Rebecca Kondor David E Wentworth Lynne Whittaker Burcu Ermetal Rodney Stuart Daniels John McCauley Seiichiro Fujisaki Kazuya Nakamura Noriko Kishida Shinji Watanabe Hideki Hasegawa Ian Barr Kanta Subbarao Pierre Barrat-Charlaix Richard A Neher Trevor Bedford
Seasonal influenza virus A/H3N2 is a major cause of death globally. Vaccination remains the most effective preventative. Rapid mutation of hemagglutinin allows viruses to escape adaptive immunity. This antigenic drift necessitates regular vaccine updates. Effective vaccine strains need to represent H3N2 populations circulating one year after strain selection. Experts select strains based on experimental measurements of antigenic drift and predictions made by models from hemagglutinin sequences. We developed a novel influenza forecasting framework that integrates phenotypic measures of antigenic drift and functional constraint with previously published sequence-only fitness estimates. Forecasts informed by phenotypic measures of antigenic drift consistently outperformed previous sequence- only estimates, while sequence-only estimates of functional constraint surpassed more comprehensive experimentally-informed estimates. Importantly, the best models integrated estimates of both functional constraint and either antigenic drift phenotypes or recent population growth.