De Novo Immune Induction After COVID-19 Vaccination Under B-Cell Depletion Is Characterized by Robust T-Cellular Immunity in Patients With Inflammatory Central Nervous System Disease

Abstract

Background: Immune induction under B-cell depletion is complex and far from being fully understood. Methods: We investigated clinical and immunological responses after dual homologous mRNA vaccination with BNT162b2 and after booster vaccination or infection in 14 B-cell depleted patients with inflammatory central nervous system disease in comparison to 28 healthy controls. Spike-specific IgG were determined using ELISA and neutralizing activity by surrogate assay. Reactive T cells were flow-cytometrically analyzed after spike-specific and polyclonal stimulation. Reactogenicity was self-reported using a questionnaire. Results: Vaccination was well tolerated, with slightly more systemic events reported by patients. Spike-specific antibodies were induced in all controls, but only 43% of patients with significantly lower IgG levels and reduced neutralizing capacity (p < 0.0001). In contrast, spike-reactive T cells were induced in both groups with similar CD4 and higher CD8 T-cell levels in patients. Functional characterization of spike-reactive T cells revealed equally high CTLA-4 expression in both groups, but higher proportions of polyfunctional, triple-cytokine expressing CD4 and CD8 T cells in patients especially after the third immunization. Three patients experienced mild breakthrough infections after second vaccination. Conclusions: Despite limited ability of B-cell depleted patients to mount a humoral immune response after multiple doses of SARS-CoV-2 mRNA vaccination, the vaccine-induced T-cell response is robust, which may have implications for protection against severe disease.