Humoral and Cellular Immunity for TBE Vaccination in Allogeneic HSCT Recipients
Condition: Tick Borne Encephalitis
MeSH terms: Encephalitis, Tick-Borne; Encephalitis
Intervention: TBE virus vaccine
Intervention description: TBE virus vaccine FSME Immun is used in both arms for the study population and the control group
Phase: Phase 2
Study type: Interventional
Primary purpose: Prevention
Allocation: Non-Randomized
Intervention model: Parallel Assignment
Masking: None (Open Label)
Enrollment: 34.0
Sex: All
Minimum age: 18 Years
Healthy volunteers: Accepts Healthy Volunteers
Keywords: Marrow transplant recipients

Summary:

      Patients undergoing allogeneic blood and marrow transplantation (HSCT) experience a prolonged
      period of dysfunctional immunity. Systematic reimmunization is necessary at appropriate time
      intervals following transplantation to re-establish immunity. Vaccination practices after
      HSCT remain varied and data sparse. Tick-borne encephalitis (TBE) is one of the most severe
      infections of the central nervous system caused by a tick-borne flavivirus. There is no
      specific treatment, and prevention with the vaccine is the only intervention available. To
      assess the efficacy of TBE vaccination in adult allogeneic HSCT recipients compared to an
      age-matched and sex-matched control group of healthy volunteers without previous TBE
      vaccination, a prospective open-label phase II pilot study on humoral and cellular immune
      responses after use of TBE vaccine (FSME Immun) will be performed. As primary end point the
      outcome of the neutralization test (NT) against TBE will be assessed in a total of 26 HSCT
      patients one year after HSCT and in 26 healthy volunteers, namely four weeks after the second
      vaccination. Therefore, the number of subjects with NT titres against TBE virus >10, assumed
      to be the threshold for antibody-mediated protection will be evaluated. As secondary
      endpoints, antibody concentrations of TBE enzyme-linked immunosorbent assay before and four
      weeks after the second and third vaccination and antibody concentrations of NT against TBE
      four weeks after primary immunization. To evaluate cellular immune responses, lymphocyte
      proliferations assays and cytokine detection assays will be performed. In a subgroup
      analysis, these secondary endpoints will be compared between healthy volunteers, HSCT
      patients without immunosuppressive treatment and HSCT patients receiving immunosuppressive
      agents. Additionally, immune reconstitution by analysis of peripheral blood lymphocyte
      subsets and serum immunoglobulin levels will be evaluated prior to vaccination, after twelve
      weeks and prior to the third vaccination in HSCT patients only.
    

Eligibility criteria:

        Inclusion Criteria:

          -  Male and female subjects will be eligible for participation in this study if they:

               -  Are ≥18 years on the day of screening

               -  Had undergone an allogeneic HSCT 11 to 13 months ago (study population)

               -  Are clinical healthy without previous TBE vaccination (control group)

               -  Have an understanding of the study, agree to its provisions, and give written
                  informed consent prior to study entry

               -  If female and capable of bearing children - have a negative urine pregnancy test
                  result at study entry and agree to employ adequate birth control measures for the
                  duration of the study

        Exclusion Criteria:

          -  Subjects will be excluded from participation in this study if they:

               -  Have received a TBE vaccination following HSCT

               -  Suffer from extremely severe acute graft-versus host disease and therefore
                  receive prednisone >0.5 mg/kg bodyweight as part of a combination therapy or a
                  three agent immunosuppressive treatment (because in these HSCT patients any type
                  of vaccination has to be postponed until immunosuppression is reduced to a double
                  combination or prednisone <0.5 mg/kg bodyweight)

               -  Suffer from or have a history of previous TBE virus infection or vaccination,
                  previous dengue virus infection or vaccination against yellow fever or Japanese
                  encephalitis

               -  Have any acute febrile illness in the 2 weeks prior to or at the time of
                  enrolment

               -  Have a history of severe allergic reactions or anaphylaxis after vaccination

               -  If female, are pregnant or lactating.

               -  If belonging to the healthy control group, are immunosuppressed (suffer from or
                  have a history of immune mediated diseases, long-term use of corticosteroids,
                  hemodialysis, chronic renal insufficiency, liver cirrhosis Child-Pugh class C,
                  hematooncological malignant disease, solid organ transplant, HSCT)