Humoral- and T-Cell–Specific Immune Responses to SARS-CoV-2 mRNA Vaccination in Patients With MS Using Different Disease-Modifying Therapies

Abstract

Objective:To evaluate the immune-specific response after the full SARS-CoV-2 vaccination of multiple sclerosis (MS) patients treated with different Disease Modifying drugs by the detection of both serological- and T-cell responses.Methods:Health care workers (HCWs) and MS patients, having completed the two-dose schedule of an mRNA-based vaccine against SARS-CoV-2 in the last 2-4 weeks, were enrolled from two parallel prospective studies conducted in Rome, Italy, at the National Institute for Infectious diseases Spallanzani–IRCSS and San Camillo Forlanini Hospital. Serological response was evaluated by quantifying the Region-Binding-Domain (RBD) and neutralizing-antibodies. Cell-mediated response was analyzed by a whole-blood test quantifying interferon (IFN)-γ response to spike peptides. Cells responding to spike stimulation were identified by FACS analysis.Results:We prospectively enrolled 186 vaccinated individuals: 78 HCWs and 108 MS patients. Twenty-eight MS patients were treated with IFN-β, 35 with fingolimod, 20 with cladribine, and 25 with ocrelizumab. A lower anti-RBD-antibody response rate was found in patients treated with ocrelizumab (40%, p<0.0001) and fingolimod (85.7%, p=0.0023) compared to HCWs and patients treated with cladribine or IFN-β. Anti-RBD-antibody median titer was lower in patients treated with ocrelizumab (p<0.0001), fingolimod (p<0.0001) and cladribine (p=0.010) compared to HCWs and IFN-β-treated patients. Importantly, serum neutralizing activity was present in all the HCWs tested and only in a minority of the fingolimod-treated patients (16.6%). T-cell-specific response was detected in the majority of MS patients (62%), albeit with significantly lower IFN-γ levels compared to HCWs. The lowest frequency of T-cell response was found in fingolimod-treated patients (14.3%). T-cell-specific response correlated with lymphocyte count and anti-RBD antibody titer (rho=0.554, p<0.0001 and rho=0.255, p=0.0078 respectively). Finally, IFN-γ T-cell response was mediated by both CD4+ and CD8+ T cells.Conclusion:mRNA vaccines induce both humoral and cell-mediated specific immune responses against spike peptides in all HCWs and in the majority of MS patients. These results carry relevant implications for managing vaccinations suggesting to promote vaccination in all treated MS patients.Classification of Evidence:This study provides Class III data that COVID mRNA vaccination induces both humoral and cell-mediated specific immune responses against viral spike proteins in a majority of MS patients.

Immune response to SARS-CoV-2 vaccination in relation to peripheral immune cell profiles among patients with multiple sclerosis receiving ocrelizumab

“…In contrast, anti-SARS-CoV-2-ab response was previously found in the majority of patients with MS on other DMTs (eg, fingolimod 85.7%, IFN-β 96.4% and cladribine 100%). 32 As expected, anti-SARS-CoV-2(S)-abs correlated with the amount of peripheral B cells in OCR-treated patients with MS. This is in line with previous observations in patients receiving B cell-modulating therapies.…”

“… 12 14 As opposed to the low percentage of patients who developed anti-SARS-CoV-2-abs after vaccination, the SARS-CoV-2-specific T cell response seems to be higher in OCR-treated patients with MS compared with patients receiving other DMTs (eg, IFN-β 89.3%, cladribine 70% and fingolimod 14.3% of patients). 32 Of note, IFN-γ release by SARS-CoV-specific T cells was even more pronounced in OCR-treated patients with MS without anti-SARS-CoV-2-abs which might point towards a compensatory effect for the insufficient humoral immune response. IFN-γ release correlated with peripheral CD3 and CD4 lymphocyte counts, but no correlation with CD8 lymphocytes was observed.…”

SARS-CoV-2 mRNA Vaccination in People with Multiple Sclerosis Treated with Fingolimod: Protective Humoral Immune Responses May Develop after the Preferred Third Shot

“…Indeed, several reports corroborated that vaccination on treatment with S1PR modulators are associated with reduced seroconversion rates and attenuated responses [17][18][19]. This observation was also extended to mRNA vaccines against SARS-CoV-2 [20][21][22][23][24].…”

Kinetics of the B- and T-Cell Immune Responses After 6 Months From SARS-CoV-2 mRNA Vaccination in Patients With Rheumatoid Arthritis

“…To evaluate the specific IFN-g-Spike (S)-specific T-cell response, a whole-blood platform was used (20,(23)(24)(25)(26)(27)(28)(29). We stimulated the whole blood with a pool of peptides that covered the SARS-CoV-2-S protein sequence (SARS-CoV-2 PepTivator ® Prot_S1, Prot_S, and Prot_S+, cat.…”