COVID-19 Vaccine Response in Treated MS Patients
Condition: Multiple Sclerosis; Healthy
MeSH terms: Multiple Sclerosis; Sclerosis
Study type: Observational

Summary: 
      The primary goal of this study is to assess the impact of the two major disease modifying
      therapy (DMT) classes (B cell therapies and S1P modulators) on humoral and cell-mediated
      immunity to SARS- CoV-2 vaccination compared to non-MS controls. We have chosen to compare
      DMT-treated MS patients to non-MS controls because the pivotal vaccine studies were conducted
      in non-MS healthy control groups in which there is significant clinical data and validated
      assays for antibody responses.
    

Detailed description: 
      Multiple sclerosis (MS) affects approximately 1 million persons in the United States and is
      the leading cause of disability in young adults. Disease modifying treatments for MS act
      through modulation or suppression of immune responses including B and T cell responses. Two
      major classes of drugs used to treat MS are 1) B cell antibodies, including Kesimpta
      (ofatumumab) and Ocrevus (ocrelizumab), and 2) S1P (sphingosine-1-phosphate) modulators
      including Gilenya (fingolimod) and Mayzent (siponimod). SARS-CoV2 is a potentially fatal
      novel coronavirus, which has claimed over 350,000 lives in the United States. The causative
      agent of COVID-19 disease, the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2)
      utilizes the angiotensin converting enzyme II (ACE2) to target cells in the lower airway.(1,
      2) Symptoms of COVID-19 infection can cause pneumonia with primarily lymphocytic inflammatory
      infiltrates.(3) Most people (approximately 81%) experience mild upper respiratory tract
      infection or mild pneumonia, while approximately 15-20% of cases experience severe or
      critical disease characterized by dyspnea, lung infiltrates, respiratory failure and multiple
      organ dysfunction.(4) The case- fatality rate ranges from 0.7-5.8%. SARS-CoV2 vaccines have
      just been FDA approved, including the Moderna® and Pfizer-BioNTech® vaccines which contain
      lipid nanoparticle- formulated nucleoside-modified mRNA (messenger ribonucleic acid) that
      encodes the receptor binding domain (RBD) of the SARS-CoV-2 spike protein.(5, 6) Prior work
      suggests that vaccine responses may be blunted in patients treated with these two drug
      classes, however there is currently no controlled data on the efficacy and durability of
      SARS-CoV2 vaccine responses in treated MS patients. Current data is limited to uncontrolled
      case reports.

      Robust studies are needed to inform the efficacy of SARS-CoV2 vaccines in MS patients on
      DMTs, which will guide infection risk management.

      The primary goal of this study is to assess the impact of the two major DMT classes (B cell
      therapies and S1P modulators) on humoral and cell-mediated immunity to SARS- CoV-2
      vaccination compared to non-MS controls. We have chosen to compare DMT-treated MS patients to
      non-MS controls because the pivotal vaccine studies were conducted in non-MS healthy control
      groups in which there is significant clinical data and validated assays for antibody
      responses.

      The primary endpoint of this study is to compare the percentage of MS patients on
      immunotherapy with a positive SARS-CoV-2 Spike antibody response (positive seroconversion)
      compared to the percentage of controls who seroconvert at 5-6 months post vaccination.

      Secondary endpoints of this study are:

        -  Comparison of SARS-CoV-2 Spike antibody % seroconversion and titers in MS patients on
           immunotherapy to titers in controls at 2-3 months and 11-12 months post vaccination.

        -  Comparison of T cell responses to SARS-CoV-2 spike protein in MS patients on
           immunotherapy to titers in controls at 5-6 months post vaccination.

        -  Comparison of antibody titers and T cell responses between the four groups of
           immunotherapies evaluated and to controls at each of the three timepoints.
    

Intervention name(s): Blood draw
Intervention type(s): Other
Intervention description(s): Approximately 120 mL whole blood will be collected from each subject at each timepoint
Observational model: Cohort
Time perspective: Prospective
Sampling method: Non-Probability Sample
Study population: 
        For this study, we will prospectively collect data and biospecimens from MS patients and
        healthy volunteers. MS patients will largely be recruited from the Brigham MS Center at
        Brigham and Women's Hospital (Boston MA US). Healthy volunteers will be recruited from the
        community surrounding BWH and through IRB-approved recruitment advertisements. The Brigham
        MS Center sees 2500 patients annually and is adjacent to an ongoing COVID vaccine clinic.
      
Biospecimen description: 
      Approximately 120 mL whole blood will be collected from each subject at each timepoint: 20 mL
      will be sent to the BWH clinical laboratories for same day SARS-CoV2 antibody assays and
      immunoglobulin levels. Additional blood for research immune assays will be collected and
      stored: 60-70 mL will be collected in cell preparation tubes (CPTs) for peripheral blood
      mononuclear cell (PBMC) isolation, 10 mL for DNA isolation and 20 mL by serum separator tubes
      for serum collection using a standardized sample collection kit. PBMCs will isolated and
      stored in liquid nitrogen and serum will be frozen at -80 °C.
    
Keywords: Multiple Sclerosis; COVID-19; mRNA vaccine