Baseline immunotypes reveal weak and strong antibody responders to influenza vaccination

Abstract Vaccines are currently the best available interventions to protect individuals from infectious diseases. However, immunosenescence, described as immune dysfunction at older age, leads to lower responsiveness to vaccines. We analyzed a broad set of immune cell subsets (n=129) in whole-blood of 308 individuals (aged 25–98) pre- and post-flu vaccination to identify those with decreased vaccine responsiveness. Detailed T, B, NK cell and monocyte subsets were examined and associated with day 28 hemagglutination inhibition antibody titers. None of the 129 immune cell subsets at day 0 associated with antibody titers (FDR adj.p>0.05). Previously, based on 59 immune cell subsets we stratified individuals using an unsupervised approach into 9 immune clusters which we named immunotypes. We identified two specific immunotypes that were associated with either a significantly weak and or a strong antibody response 28 days after vaccination. These weak responders were characterized by a lower CD4+ T naïve/memory (Tn/Tm) cell ratio, lower percentage of non-classical (anti-inflammatory) monocytes and higher number & percentage of HLA-DR+ CD4+ & CD8+ T cells, a clear ageing-related immune signature. In contrast, strong responders showed a higher Tn/Tm ratio and higher percentage of stem cell like memory CD4+ & CD8+ T cells. A weak antibody response was also associated with a lower percentage of follicular HLA-DR+ and follicular CD38+ T cells, and higher CD4+ T effector regulatory cells 7 days after vaccination. Overall, we identified pre-vaccination immunotypes that were associated with distinct vaccine responsiveness profiles that may be useful for future risk profiling