Serum IgA immune-history profiles are novel correlates of risk and protection for influenza infection

Seasonal influenza vaccination significantly reduces the risk of infection with efficacy varying by year. A key factor in determining an individual’s response to vaccination is ‘immune history’ – the memory antibody repertoire against previously encountered pathogens and vaccines.
To study the role of influenza immune-history, we developed a novel influenza antigen microarray spotted with whole-inactivated influenza viruses, recombinant surface glcyoproteins and their respective overlapping peptides. Viruses from influenza A H3N2, H1N1 and B subtypes were included. We used serum samples of a case-control set of 162 subjects from FluVacs – a randomized double-blind placebo-controlled influenza vaccine efficacy trial comparing the inactivated (IIV) and live-attenuated (LAIV) vaccines in 2000 adults aged 18-65, conducted in 2007-2008. Samples were collected at 3 timepoints: baseline (d0), post-vaccination (d21) and end-of-season (d90).
Antibody profiles were measured for all subjects. We observed a high heterogeneity of responses to influenza strains at baseline and divided them to high-, medium- and low-responders. We found that IgA low-responders in both the placebo and vaccine arms had infection rates >80%. In contrast, IgA high responders had infection rates of 22% in placebos and 0% in IIV vaccinated subjects. Stratifying individuals based on their post-vaccination responses identified additional vaccinated subjects that were at high or low risk to acquire infection. Our data suggests that serum IgA immune-history profiles are novel correlates of risk and protection for influenza infection, and that individuals can be stratified at baseline to identify a sub-population of low-responders who are at high risk of acquiring influenza infection.