Integrating genotypes and phenotypes improves long-term forecasts of seasonal influenza A/H3N2 evolution.
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.
['Huddleston|John|J|0000-0002-4250-2063', 'Barnes|John R|JR|', 'Rowe|Thomas|T|', 'Xu|Xiyan|X|', 'Kondor|Rebecca|R|0000-0002-2596-4282', 'Wentworth|David E|DE|0000-0002-5190-980X', 'Whittaker|Lynne|L|', 'Ermetal|Burcu|B|', 'Daniels|Rodney Stuart|RS|', 'McCauley|John W|JW|0000-0002-4744-6347', 'Fujisaki|Seiichiro|S|', 'Nakamura|Kazuya|K|', 'Kishida|Noriko|N|', 'Watanabe|Shinji|S|', 'Hasegawa|Hideki|H|', 'Barr|Ian|I|', 'Subbarao|Kanta|K|0000-0003-1713-3056', 'Barrat-Charlaix|Pierre|P|0000-0002-3816-3724', 'Neher|Richard A|RA|0000-0003-2525-1407', 'Bedford|Trevor|T|0000-0002-4039-5794']
D005544:Forecasting D005838:Genotype D006801:Humans D053122:Influenza A Virus, H3N2 Subtype D007251:Influenza, Human D010641:Phenotype D012621:Seasons
phenotypes influenza evolution virus antigenic drift prediction evolutionary biology infectious disease microbiology