دورية أكاديمية
Longitudinal adaptive immune responses following sequential SARS-CoV-2 vaccinations in MS patients on anti-CD20 therapies and sphingosine-1-phosphate receptor modulators.
| العنوان: | Longitudinal adaptive immune responses following sequential SARS-CoV-2 vaccinations in MS patients on anti-CD20 therapies and sphingosine-1-phosphate receptor modulators. |
|---|---|
| المؤلفون: | Sabatino JJ Jr; UCSF Weill Institute for Neurosciences, Department of Neurology, University of California, San Francisco, CA, USA., Mittl K; UCSF Weill Institute for Neurosciences, Department of Neurology, University of California, San Francisco, CA, USA., Rowles W; UCSF Weill Institute for Neurosciences, Department of Neurology, University of California, San Francisco, CA, USA., Zamecnik CR; UCSF Weill Institute for Neurosciences, Department of Neurology, University of California, San Francisco, CA, USA., Loudermilk RP; UCSF Weill Institute for Neurosciences, Department of Neurology, University of California, San Francisco, CA, USA., Gerungan C; UCSF Weill Institute for Neurosciences, Department of Neurology, University of California, San Francisco, CA, USA., Spencer CM; UCSF Weill Institute for Neurosciences, Department of Neurology, University of California, San Francisco, CA, USA., Sagan SA; UCSF Weill Institute for Neurosciences, Department of Neurology, University of California, San Francisco, CA, USA., Alexander J; UCSF Weill Institute for Neurosciences, Department of Neurology, University of California, San Francisco, CA, USA., Mcpolin K; UCSF Weill Institute for Neurosciences, Department of Neurology, University of California, San Francisco, CA, USA., Chen P; UCSF Weill Institute for Neurosciences, Department of Neurology, University of California, San Francisco, CA, USA., Deshpande C; Novartis Pharmaceuticals, East Hanover, NJ, USA., Wyse K; Novartis Pharmaceuticals, East Hanover, NJ, USA., Maiese EM; Novartis Pharmaceuticals, East Hanover, NJ, USA., Wilson MR; UCSF Weill Institute for Neurosciences, Department of Neurology, University of California, San Francisco, CA, USA., Zamvil SS; UCSF Weill Institute for Neurosciences, Department of Neurology, University of California, San Francisco, CA, USA., Bove R; UCSF Weill Institute for Neurosciences, Department of Neurology, University of California, San Francisco, CA, USA. Electronic address: riley.bove@ucsf.edu. |
| المصدر: | Multiple sclerosis and related disorders [Mult Scler Relat Disord] 2023 Feb; Vol. 70, pp. 104484. Date of Electronic Publication: 2022 Dec 28. |
| نوع المنشور: | Observational Study; Journal Article |
| اللغة: | English |
| بيانات الدورية: | Publisher: Elsevier B. V Country of Publication: Netherlands NLM ID: 101580247 Publication Model: Print-Electronic Cited Medium: Internet ISSN: 2211-0356 (Electronic) Linking ISSN: 22110348 NLM ISO Abbreviation: Mult Scler Relat Disord Subsets: MEDLINE |
| أسماء مطبوعة: | Original Publication: [Amsterdam] : Elsevier B. V. |
| مواضيع طبية MeSH: | Sphingosine 1 Phosphate Receptor Modulators* , COVID-19* , Multiple Sclerosis*, Humans ; Immunity, Humoral ; COVID-19 Vaccines ; Sphingosine-1-Phosphate Receptors ; SARS-CoV-2 ; Longitudinal Studies ; Pandemics ; Vaccination ; Antibodies, Monoclonal ; Immunoglobulin G ; Antibodies, Viral |
| مستخلص: | Background: Adequate response to the SARS-CoV-2 vaccine represents an important treatment goal in caring for patients with multiple sclerosis (MS) during the ongoing COVID-19 pandemic. Previous data so far have demonstrated lower spike-specific IgG responses following two SARS-CoV-2 vaccinations in MS patients treated with sphingosine-1-phosphate (S1P) receptor modulators and anti-CD20 monoclonal antibodies (mAb) compared to other disease modifying therapies (DMTs). It is unknown whether subsequent vaccinations can augment antibody responses in these patients. Objectives: The goal of this observational study was to determine the effects of a third SARS-CoV-2 vaccination on antibody and T cell responses in MS patients treated with anti-CD20 mAb or S1P receptor modulators. Methods: Vaccine responses in patients treated with anti-CD20 antibodies (ocrelizumab and ofatumumab) or S1P receptor modulators (fingolimod and siponimod) were evaluated before and after third SARS-CoV-2 vaccination as part of an ongoing longitudinal study. Total spike protein and spike receptor binding domain (RBD)-specific IgG responses were measured by Luminex bead-based assay. Spike-specific CD4+ and CD8+ T cell responses were measured by activation-induced marker expression. Results: MS patients and healthy controls were enrolled before and following SARS-CoV-2 vaccination. A total of 31 MS patients (n = 10 ofatumumab, n = 13 ocrelizumab, n = 8 S1P) and 10 healthy controls were evaluated through three SARS-CoV-2 vaccinations. Compared to healthy controls, total spike IgG was significantly lower in anti-CD20 mAb-treated patients and spike RBD IgG was significantly lower in anti-CD20 mAb and S1P-treated patients following a third vaccination. While seropositivity was 100% in healthy controls after a third vaccination, total spike IgG and spike RBD IgG seropositivity were lower in ofatumumab (60% and 60%, respectively), ocrelizumab (85% and 46%, respectively), and S1P-treated patients (100% and 75%, respectively). Longer treatment duration, including prior treatment history, appeared to negatively impact antibody responses. Spike-specific CD4+ and CD8+ T cell responses were well maintained across all groups following a third vaccination. Finally, immune responses were also compared in patients who were vaccinated prior to or following ofatumumab treatment. Antibody responses were significantly higher in those patients who received their primary SARS-CoV-2 vaccination prior to initiating ofatumumab treatment. Conclusions: This study adds to the evolving understanding of SARS-CoV-2 vaccine responses in people with MS treated with disease-modifying therapies (DMTs) known to suppress humoral immunity. Our findings provide important information for optimizing vaccine immunity in at-risk MS patient populations. (Copyright © 2022. Published by Elsevier B.V.) |
| معلومات مُعتمدة: | R01 AI131624 United States AI NIAID NIH HHS; R35 NS111644 United States NS NINDS NIH HHS |
| فهرسة مساهمة: | Keywords: COVID-19; Disease modifying therapy; Multiple sclerosis; SARS-COV-2; Vaccine |
| المشرفين على المادة: | 0 (Sphingosine 1 Phosphate Receptor Modulators) 0 (COVID-19 Vaccines) 0 (Sphingosine-1-Phosphate Receptors) 0 (Antibodies, Monoclonal) 0 (Immunoglobulin G) 0 (Antibodies, Viral) |
| تواريخ الأحداث: | Date Created: 20230106 Date Completed: 20230314 Latest Revision: 20240222 |
| رمز التحديث: | 20240222 |
| مُعرف محوري في PubMed: | PMC9794398 |
| DOI: | 10.1016/j.msard.2022.104484 |
| PMID: | 36608538 |
| قاعدة البيانات: | MEDLINE |
Full Text via ClinicalKey 
Full Text Finder | تدمد: | 2211-0356 |
|---|---|
| DOI: | 10.1016/j.msard.2022.104484 |