摘要：SummaryThe elderly are an important target for influenza vaccination, and the determination of factors that underlie immune responsiveness is clinically valuable. We evaluated the immune and metabolic profiles of 205 elderly Singaporeans administered with Vaxigrip. Despite high seroprotection rates, we observed heterogeneity in the response. We stratified the cohort into complete (CR) or incomplete responders (IR), where IR exhibited signs of accelerated T cell aging. We found a higher upregulation of genes associated with the B-cell endoplasmic-reticulum stress response in CR, where XBP-1 acts as a key upstream regulator. B-cells from IR were incapable of matching the level of XBP-1 upregulation observed in CR after inducing ER stress with tunicamycinin vitro. Metabolic signatures also distinguished CR and IR – as CR presented with a greater diversity of bile acids. Our findings suggest that the ER-stress pathway activation could improve influenza vaccination in the elderly.Graphical abstractDisplay OmittedHighlights•Seroprotected elderly had heterogeneous titre responses to all three influenza strains•Multi-strain responses are linked to distinct transcriptomic and bile acid profiles•XBP-1 related pathways are specifically enriched in complete responders•XBP-1 upregulation is better preserved in vaccinated complete respondersImmunology; Virology; Clinical microbiology; Cell biology
