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Multiple Sclerosis Journal ; 27(2 SUPPL):789, 2021.
Article in English | EMBASE | ID: covidwho-1496060


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.

Multiple Sclerosis Journal ; 27(2 SUPPL):562-563, 2021.
Article in English | EMBASE | ID: covidwho-1495938


Background: Data on the effects of multiple sclerosis (MS) disease modifying therapies (DMTs) on SARS-CoV-2 vaccine response are needed. Initial studies suggest CD20 cell depleting therapies and fingolimod attenuate IgG response to SARS-CoV-2 vaccination in MS patients (pts), consistent with previous studies of vaccine responses in pts treated with those DMTs. Methods: Participants with MS enrolled in the MS PATHS network in the US, Germany, and Spain were asked to provide blood serum samples up to 30 days pre-SARS-CoV-2 vaccination and 28-90 days post final vaccine dose. The goal is to obtain & ge;45 post-vaccination samples per approved DMT and among pts not currently treated with a DMT. Semi-quantitative measures of SARS-CoV-2 IgG response to spike protein (Siemens SARSCoV- 2 IgG assay) and nucleocapsid protein (Abbott SARS-CoV-2 IgG assay) will be used to distinguish humoral responses to vaccination vs prior infection. The impact of demographic factors, MS disease subtype and duration, disability level, DMT type, vaccine type, and time since last DMT dose, and vaccine dose on IgG response will be evaluated. Results: As of May 17, 2021, 379 unique pts provided a serum sample: CD20 DMTs (n=139), S1P DMTs (n=31), natalizumab (n=39), other DMTs (n=117), and no DMT (n=53);183 pts have a pre-vaccination sample awaiting a post-vaccination sample, 186 have only a post-vaccination sample, and 10 have both. Prevaccination samples were collected at a mean (SD) of 4.5 (7.5) days prior to the first vaccine dose, and post-vaccination samples were collected 46.6 (15.2) days after the last dose, 91.8% following an mRNA vaccine. Pt (n=379) characteristics were: age 50.3 (12.5) yrs, 67% female, disease duration 16.6 (9.6) yrs, 27.7% progressive MS, and Patient Determined Disease Steps 2.0 (2.3). Reactive IgG rates (IgG index & gt;1) from initial post-vaccination testing were CD20 DMTs 21/41 (51%), S1P DMTs 4/8 (50%), and 100% for all other groups, including natalizumab (n=9), fumarates (n=8), interferons (n=8), glatiramer acetate (n=8), teriflunomide (n=2), alemtuzumab (n=1) and no DMT (n=17). Conclusions: Preliminary results, based on a limited sample size, suggest CD20 and S1P DMTs may reduce IgG response to SARS-CoV-2 vaccination. Quantifying post-vaccination IgG response across DMTs is crucial to optimize MS management. Data from ongoing sample collection will be presented at the meeting.