Antibody and T cell subsets analysis unveils an immune profile heterogeneity mediating long-term responses in individuals vaccinated against SARS-CoV-2.

BACKGROUND: Based on the fact that COVID-19 is still spreading despite vaccine worldwide administration, there is an imperative need to understand the underlying mechanisms of vaccine-induced inter-individual immune response variations. METHODS: We compared humoral and cellular immune responses in 127 individuals vaccinated with either BNT162b2, mRNA-1273 or ChAdOx1-nCoV-19 vaccine. RESULTS: We found that both mRNA vaccines induced faster and stronger humoral responses as assessed by high Spike- and RBD-specific antibody titers and neutralizing efficacy in comparison to ChAdOx1-nCoV-19 vaccine. At 7 months post vaccination, a decreasing trend in humoral responses was observed, irrespective of the vaccine administered. Correlation analysis between anti-S1 IgG and IFNγ production unveiled a heterogeneous immune profile among BNT162b2-vaccinated individuals. Specifically, vaccination in the high-responder group induced sizable populations of polyfunctional memory CD4+ TH1 cells, follicular helper T cells (TFH) and T cells with features of stemness along with high neutralizing antibody production that persisted up to 7 months.. In contrast, low responders were characterized by loss or significantly reduced antibody titers and memory T cells and a considerably lower capacity for IL-2 and IFNγ production. CONCLUSIONS: We identified that long-term humoral responses correlate with the individual's ability to produce antigen-specific persistent memory T cell populations.