De Novo Immune Induction After COVID-19 Vaccination Under B-Cell Depletion Is Characterized by Robust T-Cellular...

Immune induction under B-cell depletion is complex and far from being fully understood.

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.

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.

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.