Assessing evidence of immune imprinting in serological patterns of influenza immune response

The subtype of the first influenza infection shapes infection risk, illness and mortality associated with subsequent infection subtypes, as well as vaccine efficacy. This phenomenon, termed ‘immune imprinting’, may result from immune recognition rooted in structural similarity of the hemagglutinin protein within subtypes of influenza viruses. However, it is difficult to isolate from cohort effects resulting from the annual dominance of specific influenza subtypes. We used a long-term cohort study in southern China to examine whether hemagglutination inhibition responses show evidence of imprinting, and explore whether such patterns could emerge in the absence of imprinting using simulations. Our statistical analysis reveals patterns consistent with immune imprinting. However, simulations showed that similar patterns can emerge without an imprinting mechanism, meaning these may partly be due to age-related variations in immune responses driven by other factors. This work lays the foundations for further research into immune imprinting while accounting for cohort effects.