RESEARCH ARTICLE Estimating the Life Course of Influenza A (H3N2) Antibody Responses from Cross- Sectional Data

The immunity of a host population against specific influenza A strains can influence a number of important biological processes, from the emergence of new virus strains to the effectiveness of vaccination programmes. However, the development of an individual’s long-lived antibody response to influenza A over the course of a lifetime remains poorly un-derstood. Accurately describing this immunological process requires a fundamental under-standing of how the mechanisms of boosting and cross-reactivity respond to repeated infections. Establishing the contribution of such mechanisms to antibody titres remains chal-lenging because the aggregate effect of immune responses over a lifetime are rarely ob-served directly. To uncover the aggregate effect of multiple influenza infections, we developed a mechanistic model capturing both past infections and subsequent antibody re-sponses. We estimated parameters of the model using cross-sectional antibody titres to nine different strains spanning 40 years of circulation of influenza A(H3N2) in southern China. We found that “antigenic seniority ” and quickly decaying cross-reactivity were impor-tant components of the immune response, suggesting that the order in which individual