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

The mechanism behind the positive association between immunity to non-recent strains and seroconversion to recent strains is unclear. One plausible hypothesis is that a subset of people tend to have a more vigorous titer response across strains (e.g. individual heterogeneity in immune responses). This is supported by our data that positive association can still be detected when using titer to an older strain, instead of the summary metric of antibody profiles, as the proxy of immunity to non-recent strains (fig. S14). Another plausible hypothesis is that non-HAI immunity that was acquired from previous infections (e.g. antibody to HA stalk and NA and cellular immune responses) could blunt the production of strain-specific antibody upon exposure to circulating strains (18) (19) (20) (21) , thus reducing the HAI titers to the circulating strains and increasing the probability of seroconversion. High antibody to non-recent strains could indicate individuals who have not experienced infection in recent times [e.g. low strain-specific antibody to currently circulating strains due to temporary protection from last infection; (23, 26, 27) ]. Homologous HAI titers may reflect the combined binding ability of antibody targeting the tested antigen as well as antibody targeting previously encountered epitopes, and high antibody titers to non-recent strains may indicate particular distributions of these two that are less protective.