Investigating Mechanism of Action of DAC HYP in the Treatment of High-Inflammatory Multiple Sclerosis (MS)

* The study population will consist of 2 cohorts of patients with an accrual ceiling of 40 subjects: A. Long-term daclizumab therapy cohort: Up to 16 patients with HI-MS (both RR-MS and SP-MS) who have been successfully treated with IV daclizumab for a minimum of 1 year. B. New treatment cohort: Up to 15 patients with HI-MS (both RR-MS and SP-MS) who have not been successfully treated with or have not tolerated standard FDA-approved immunomodulatory therapies, or who, for whatever reason, choose not to be treated with standard FDA approved immunomodulatory therapies. INCLUSION CRITERIA: * MS as defined by the modified McDonald criteria (Polman, Reingold et al. 2005) * HI-MS (RR-MS or SP-MS) before initiation of daclizumab therapy, defined as: * greater than or equal to 3 CEL on a single pre-daclizumab MRI or * greater than or equal to 1 MS exacerbation per year before initiation of daclizumab therapy or * progression of sustained disability by greater than or equal to 1.0 point on the expanded disability status scale (EDSS) in the year preceding daclizumab therapy * Age 18-60, inclusive * EDSS 0 to 6.0, inclusive * Able to provide informed consent * Willing to participate in all aspects of trial design and follow-up * Females of childbearing potential are willing to commit to the use of a reliable method of birth control (i.e., hormonal contraception including birth control pills, injected hormones or vaginal ring; intrauterine device; barrier methods with spermicide, specifically diaphragms or condoms they have undergone surgical sterilization, such as hysterectomy or tubal ligation) for the duration of the study and continued 4 months after conclusion of the study. ADDITIONAL INCLUSION CRITERION FOR THE LONG-TERM DACLIZUMAB THERAPY COHORT ONLY: -IV daclizumab therapy for at least 1 year with a treatment response consisting of:\<TAB\> * greater than or equal to 70% reduction of CEL after starting daclizumab; or * stabilization or improvement of sustained neurological disability on daclizumab. EXCLUSION CRITERIA (FOR BOTH COHORTS): * PP-MS or low-inflammatory SP-MS * Alternative diagnoses that can explain neurological disability and MRI findings (e.g., ischemia/gliosis, CNS lyme disease, SLE, sarcoidosis, etc.) * History of malignancy, with the following exceptions: excised or treated basal cell carcinoma or fewer than 3 squamous cell carcinomas, grade 1 endometrial carcinomas treated with total hysterectomy and without evidence for recurrence for greater than or equal to 3 years * Clinically significant medical disorders that, in the judgment of the investigators, could cause CNS tissue damage or limit its repair, expose the patient to undue risk of harm or prevent the patient from completing the study (e.g., immunodeficiency disorders, other autoimmune or immune-mediated disorders or chronic infections). Specific exclusions (based on baseline laboratory evaluation) are: * positive HIV or HTLV-1 serology; * positive hepatitis B or C serology; * pregnant or breastfeeding female; * known history of severe allergic or anaphylactic reactions; * known hypersensitivity to study drug or its excipients; * varicella or herpes zoster virus infection or any severe viral infection within the 6 weeks prior to screening; or * exposure to varicella zoster virus within 21 days before screening. * Abnormal screening/baseline blood tests exceeding any of the limits defined below: * serum alanine aminotransferase/serum glutamate pyruvate transaminase (ALT/SGPT), aspartate aminotransferase/serum glutamic oxaloacetic transaminase (AST/SGOT), or gamma-glutamyl-transferase greater than or equal to 2 times the upper limit of normal (ULN); * total white blood cell count \<3,000/mm(3); * hemoglobin greater than or equal to 9.0 g/dL; * platelets greater than or equal to 100 x 10(9)/L; * lymphocytes greater than or equal to 1.0 x 10(9)/L; * neutrophils greater than or equal to 1.5 x 10(9)/L; * serum creatinine greater than or equal to the ULN. * Any of the following treatment history: * any type of live virus vaccine in the 4 weeks prior to initiation of therapy, including but not limited to: measles/mumps/rubella vaccine, varicella zoster virus vaccine, oral polio vaccine, and nasal influenza vaccine; * infection (viral, fungal, bacterial) requiring hospitalization or intravenous (IV) antibiotics within the 8 weeks prior to initiation of therapy; * another investigational drug or approved therapy for investigational use (except daclizumab) within the 6 months prior to initiation of therapy. * Prior treatment with the any of the following: * total lymphoid irradiation; * cladribine; * T cell or T cell receptor vaccination; or * any therapeutic monoclonal antibody, except natalizumab and daclizumab. * Prior treatment with any of the following medications or procedures within 1 year prior to initiation of therapy: * mitoxantrone; * cyclophosphamide; * fingolimod; or * natalizumab. * Prior treatment with any of the following medications or procedures within 6 months prior to initiation of therapy: * cyclosporine; * azathioprine; * methotrexate; * mycophenolate mofetil; * intravenous immunoglobulin (IVIg); or * plasmapheresis or cytapheresis. * Treatment with any of the following medications within the 30 days prior to initiation of therapy: * IV corticosteroid treatment; * oral corticosteroid treatment; * glatiramer acetate; or * interferon-beta * For immunizations studies, known history of hypersensitivity or severe allergic reaction to vaccine components (subjects with such history can participate in the trial, but will not be immunized) * For patients in the extension phase: Patients may be excluded if they did not demonstrate an adequate clinical response in the first phase of the trial while receiving DAC HYP. Inclusion criteria for MS controls for immunization and skin biopsy studies: * MS as defined by the modified McDonald criteria * RR-MS or SP-MS * Age 18-60, inclusive * EDSS 0 to 7.0, inclusive * Able to provide informed consent * Willing to participate in all aspects of trial design and follow-up Exclusion criteria for MS controls for immunization and skin biopsy studies: * Treatment with immunomodulatory therapies that may have a negative impact on development of antigen-specific responses after immunization, including steroids within the last 60 days before the immunization study * Clinically significant medical disorders that, in the judgment of the investigators, could invalidate the person as appropriate control (e.g., immunodeficiency disorders, other autoimmune or immunemediated disorders or chronic infections). Specific exclusions (based on baseline laboratory evaluation) are: * positive HIV or HTLV-1 serology; * positive hepatitis B or C serology; * pregnant or breastfeeding female; * known history of severe allergic or anaphylactic reactions to vaccine components; * Abnormal screening/baseline blood tests exceeding any of the limits defined below: * serum alanine aminotransferase/serum glutamate pyruvate transaminase (ALT/SGPT), aspartate aminotransferase/serum glutamic oxaloacetic transaminase (AST/SGOT), or gamma-glutamyl-transferase (Bullet)2 times the upper limit of normal (ULN); * total white blood cell count \<3,000/mm3; * hemoglobin less than or equal to 9.0 g/dL