Quantifying the impact of pre-vaccination titre and vaccination history on influenza vaccine immunogenicity

Abstract

Epidemiological studies suggest that heterogeneity in influenza vaccine antibody response is associated with host factors, including pre-vaccination immune status, age, gender, and vaccination history. However, the pattern of reported associations varies between studies. To better understand the underlying influences on antibody responses, we combined host factors and vaccine-induced in-host antibody kinetics from a cohort study conducted across multiple seasons with a unified analysis framework. We developed a flexible Bayesian model to estimate associations and interactions between host factors, including pre-vaccine HAI titre, age, sex, vaccine history and study setting, and vaccine-induced HAI titre antibody boosting and waning. We applied the model to derive population-level and individual effects of post-vaccine antibody kinetics for vaccinating and circulating strains for A(H1N1) and A(H3N2) influenza subtypes. We found that post-vaccine HAI titre dynamics were significantly influenced by pre-vaccination HAI titre and vaccination history. In addition, we find the common heuristic of a four-fold rise in titre is valid for detecting seroconversion in an infrequently vaccinated cohort (<2 vaccines in last 5 years) within six months of vaccination if their pre-vaccination HAI titres are equal to or below 1:20. The same heuristic only works for a frequently vaccinated population (2 or more vaccines in last 5 years) for up to 3 months post-vaccination providing their pre-vaccination HAI titres are equal to or below 1:20. In future, seroepidemiological studies should ensure the impact of pre-vaccine HAI and prior vaccination status on vaccine-induced fold-rises is properly quantified, as these significantly influence an individual's post-vaccination antibody kinetics.