Back to overview

Cross-reactive immunity drives global oscillation and opposed alternation patterns of seasonal influenza A viruses

Type of publication Not peer-reviewed
Publikationsform Original article (non peer-reviewed)
Author Gatti Lorenzo, Zhang Jitao David, Anisimova Maria, Schutten Martin, Osterhaus Albert, van der Vries Erhard,
Project Fast joint estimation of alignment and phylogeny from genomic sequences in a frequentist framework
Show all

Original article (non peer-reviewed)

Journal bioRxiv
Publisher Cold Spring Harbor Laboratory
Page(s) 226613 - 226613
Title of proceedings bioRxiv
DOI 10.1002/9780470015902.a0025545

Open Access

Type of Open Access Repository (Green Open Access)


Several human pathogens exhibit distinct patterns of seasonality and circulate as pairs of discrete strains. For instance, the activity of the two co-circulating influenza A virus subtypes oscillates and peaks during winter seasons of the worlds temperate climate zones. These periods of increased activity are usually caused by a single dominant subtype. Alternation of dominant strains in successive influenza seasons makes epidemic forecasting a major challenge. From the start of the 2009 influenza pandemic we enrolled influenza A virus infected patients (n = 2,980) in a global prospective clinical study. Complete hemagglutinin (HA) sequences were obtained from 1,078 A/H1N1 and 1,033 A/H3N2 viruses and were linked to patient data. We then used phylodynamics to construct high resolution spatio-temporal phylogenetic HA trees and estimated global influenza A effective reproductive numbers (R) over time (2009-2013). We demonstrate that R, a parameter to define host immunity, oscillates around R = 1 with a clear opposed alternation pattern between phases of the A/H1N1 and A/H3N2 subtypes. Moreover, we find a similar alternation pattern for the number of global virus migration events between the sampled geographical locations. Both observations suggest a between-strain competition for susceptible hosts on a global level. Extrinsic factors that affect person-to-person transmission are a major driver of influenza seasonality, which forces influenza epidemics to coincide with winter seasons. The data presented here indicate that also cross-reactive host immunity is a key intrinsic driver of global influenza seasonality, which determines the outcome of competition between influenza A virus strains at the onset of each epidemic season.