Life course exposures continually shape antibody profile and risk of seroconversion to influenza

Bingyi Yang; Justin Lessler; Huachen Zhu; Chaoqiang Jiang; Jonathan M. Read; James A Hay; Kin On Kwok; Ruiyin Shen; Yi Guan; Steven Riley; Derek A.T. Cummings

We hypothesized that features of an antibody profile determine an individual's risk of seroconversion over and above homologous titer. We developed several metrics aimed at summarizing the information in individuals', often complex, antibody profiles (Fig. 3 ). We estimated: the area under the curve (AUC) for each antibody profile (i.e. the integral of an individual's measured log titers); the width (W z ) of an individual's antibody titer above a threshold ‫ݖ‬ (i.e. the proportion of the profile above that threshold; W 40 for protective threshold and W 10 for detectable threshold); and the average titer year (ATY) of each antibody profile (i.e. the average of strain isolation years weighted by their titer) (see Methods). We hypothesized that these features of antibody profiles captured biologically relevant properties of the immune response to H3N2; in particular, overall levels of antibody mediated immunity (for AUC), the breadth of antibody mediated immune response (for W 40 and W 10 ) and temporal center of mass of H3N2 immunity (for ATY). In most analyses, we use normalized versions of these metrics (i.e. nAUC, nW 40 , nW 10 , nATY) to adjust for differences between individuals in the number of possibly exposed strains given their ages (i.e. individuals could not have been exposed to prebirth strains) (see Methods. Non-normalized analysis included in Supplementary Materials, fig. S2 , tables S3 and S4).