Immune history to influenza infection and vaccination predicts antibody responses to the seasonal influenza vaccine

Vaccination, the most cost-effective public health intervention, stimulates the immune system to generate protective memory responses. A variety of factors impact an individual’s heterogeneity in vaccine induced immune responses, such as age and gender and ‘immunological history’ - the individual’s memory antibody repertoire to previously encountered pathogens and vaccines. Immune history is particularly interesting in influenza since humans are constantly infected and vaccinated annually. To profile the effect of immune history to previously influenza infections, we used samples form an influenza vaccine efficacy trial (FluVacs) in adults aged 18–65 conducted in 2007–2008. Samples were collected at baseline d0, post vaccination d21 and at the end of the season d90. We used antigen microarrays spotted with overlapping 20mer peptides from the HA and NA proteins of the seasonal vaccine to generate antibody profiles at baseline to represent individuals’ immune history. Profiles were also generated post-vaccination. We used unsupervised clustering to cluster profiles of individuals at baseline. We found that individuals clustered into several distinct antibody profiles. Importantly, we found that most individuals within the same baseline clusters produced similar antibody profiles post vaccination. We also compared the pre- to post-vaccination profiles and found that overall the vaccine generated a relatively modest boost of the previous antibody repertoire. Overall our results highlight the importance of profiling immune history to previous influenza infections as a baseline measurement that may be predictive of vaccine induced immune responses and vaccine-induced protection.