Longitudinal characterisation of B and T-cell immune responses after the booster dose of COVID-19 mRNA-vaccine in people with multiple sclerosis using different disease-modifying therapies

Background The decline of humoral response to COVID-19 vaccine led to authorise a booster dose. Here, we characterised the kinetics of B-cell and T-cell immune responses in patients with multiple sclerosis (PwMS) after the booster dose. Methods We enrolled 22 PwMS and 40 healthcare workers (HCWs) after 4-6 weeks from the booster dose (T3). Thirty HCWs and 19 PwMS were also recruited 6 months (T2) after the first dose. Antibody response was measured by anti-receptor-binding domain (RBD)-IgG detection, cell-mediated response by an interferon (IFN)-γrelease assay (IGRA), Th1 cytokines and T-cell memory profile by flow cytometry. Results Booster dose increased anti-RBD-IgG titers in fingolimod-treated, cladribine-treated and IFN-β-treated patients, but not in ocrelizumab-treated patients, although antibody titres were lower than HCWs. A higher number of fingolimod-treated patients seroconverted at T3. Differently, T-cell response evaluated by IGRA remained stable in PwMS independently of therapy. Spike-specific Th1-cytokine response was mainly CD4 + T-cell-mediated, and in PwMS was significantly reduced (p<0.0001) with impaired IL-2 production compared with HCWs at T3. In PwMS, total Th1 and IFN-γCD4 + T-cell responders to spike protein were increased from T2 to T3. Compared with HCWs, PwMS presented a higher frequency of CD4 + and CD8 + terminally differentiated effector memory cells and of CD4 + effector memory (T EM) cells, independently of the stimulus suggesting the association of this phenotype with MS status. CD4 + and CD8 + T EM cell frequency was further increased at T3 compared with T2. Conclusions COVID-19 vaccine booster strengthens humoral and Th1-cell responses and increases T EM cells in PwMS.