ABSTRACT
Introduction: Sphingosine-1-phosphate receptor (S1P) modulators and B cell depleting agents significantly impair humoral responses to SARS-CoV-2 mRNA vaccines. Whether disease modifying therapies (DMTs) impact cell-mediated immune (CMI) response to vaccination is unknown. Objectives/ Aims: To evaluate humoral and CMI response to SARS CoV-2 vaccination in people with MS and the impact of specific DMTs on these responses. Methods: We recruited participants from the Johns Hopkins MS center who underwent phlebotomy either 4 or 8 weeks following the terminal vaccine dose. Blood was processed to isolate serum and peripheral blood mononuclear cells (PBMCs). We measured humoral responses via an immunoassay to measure IgG against the COVID-19 spike S1 glycoprotein in serum. Blinded experimenters measured CMI responses using FluoroSpot assay for interferon gamma (IFN-γ) (Mabtech,Sweden) using cryopreserved PBMCs rested overnight and then incubated in cRPMI with 1μg/ml of pooled peptides spanning the entire spike glycoprotein (Genscript, 2 pools of 158 peptides each). Plates were read on an AID iSpot Spectrum. Results were expressed as spot forming cells (SFC)/106 PBMCs. We evaluated concordance between humoral and CMI responses and tested for differences across DMTs using linear models. Results: We included 102 participants (82% female;mean age 49.5y [SD: 10.4y];94% mRNA vaccine recipients) who were on average 6.8 weeks post-vaccine. 22/39 (56%) of participants exposed to B-cell depleting agents exhibited a humoral response to the vaccine, whereas all participants on no (n=13), injectable (n=16), or natalizumab (n=17) therapies and most (12/14;86%) on non-S1P modulating orals responded. In a subset (n=58) with CMI response data, a lack of humoral immunity was marginally associated with an 120.3% greater IFN-γ SFC counts (120.3% higher;95% CI: -25.2%, 542.4%;p=0.09). B-cell depleting agents were associated with greater IFN-γ SFC counts relative to those on no DMT or other DMTs (for B-cell vs. no DMT: 270.6% higher [95% CI: 0.0%, 1373.2%];p=0.05;for B-cell vs. other DMTs: 182.9% higher [95% CI: 15.0%, 609.9%];p=0.03). Updated CMI data with 48 additional patients will be presented. Conclusions: We noted a robust CMI response in MS patients on B-cell depleting agents despite the lack of a humoral response in about half of these patients. Follow up studies are needed to determine if this translates to protection against clinical COVID-19 infection.