Mass cytometry reveals cellular correlates of immune response heterogeneity to SARS-CoV-2 vaccination in the elderly

Abstract Heterogeneity in vaccine response, particularly in vulnerable populations like the elderly, represents a significant public health challenge. We conducted an in-depth examination of immune cell profiles before and after SARS-CoV-2 vaccination utilizing mass cytometry in a cohort of healthy Norwegian seniors (65–80 years). We have demonstrated that higher pre-vaccination frequencies of CD27⁺IgD⁻ class-switched memory B cells and subsets of CD27⁻CD24⁺CD38⁺ transitional B cells were associated with a robust vaccine response. Post-vaccination, high responders exhibited increased frequencies of IFN-γ⁺CD4⁺ T cells with antigen recall and a concurrent decrease in TH17 cell subset frequencies compared to low responders. The presence of a γδ T cell subset displaying polyfunctional cytokine responses was also associated with better vaccine response in the elderly. This comprehensive analysis sheds light on inherent differences in immune cell frequencies and functions that should offer insights for targeted vaccination strategies in older populations.