Abstract
Circulation of seasonal influenza is the product of complex interplay among multiple drivers, yet characterizing the underlying mechanism remains challenging. Leveraging the diverse seasonality of A(H3N2) virus and abundant climatic space across regions in China, we quantitatively investigated the relative importance of population susceptibility, climatic factors, and antigenic change on the dynamics of influenza A(H3N2) through an integrative modelling framework. Specifically, an absolute humidity driven multiscale transmission model was constructed for the 2013/2014, 2014/2015 and 2016/2017 influenza seasons that were dominated by influenza A(H3N2). We revealed the variable impact of absolute humidity on influenza transmission and differences in the occurring timing and magnitude of antigenic change for those three seasons. Overall, the initial population susceptibility, climatic factors, and antigenic change explained nearly 55% of variations in the dynamics of influenza A(H3N2). Specifically, the additional variation explained by the initial population susceptibility, climatic factors, and antigenic change were at 33%, 26%, and 48%, respectively. The vaccination program alone failed to fully eliminate the summer epidemics of influenza A(H3N2) and non-pharmacological interventions were needed to suppress the summer circulation. The quantitative understanding of the interplay among driving factors on the circulation of influenza A(H3N2) highlights the importance of simultaneous monitoring of fluctuations for related factors, which is crucial for precise and targeted prevention and control of seasonal influenza.