Humoral and Cellular Immunity for TBE Vaccination in Allogeneic HSCT Recipients

Learn more about:
Related Clinical Trial
The Norwegian Tick Born Encephalitis Study Study to Evaluate the Immunogenicity, Safety, and Tolerability of a Tick-Borne Encephalitis (TBE) Vaccine in Healthy Japanese Participants 1 Year of Age and Older Primary TBE Vaccination for the Elderly Application of a TBE-Vaccine in Obese Persons Safety Study of FSME-IMMUN NEW in Healthy Children and Adolescents Aged 1 to 15 Years Investigation of the Seropersistence of TBE Antibodies and the Booster Response to FSME-IMMUN 0.5 ml in Adults Aged 18 – 67 Years Dose-finding Study to Investigate the Safety and Immunogenicity of Two Vaccinations With FSME IMMUN NEW in Healthy Volunteers Aged 6 to 16 Years. Dose-finding Study to Investigate the Safety and Immunogenicity of Two Vaccinations With FSME IMMUN NEW in Healthy Volunteers Aged 1 to 6 Years. Humoral and Cellular Immunity of Low and High-responders After Tick-borne Encephalitis Vaccination Evaluation of Immunogenicity of Different Tick Borne Encephalitis (TBE) Fast Protective Traveler Schemes With Inactivated TBE Whole Virus Vaccine TBE Seropersistence up to 10 Years After First Booster in Adults Tick-borne Encephalitis and Positive Borrelial Antibodies Study to Evaluate Long Term Immunogenicity up to 10 Years After the First Booster Immunization With Tick Borne Encephalitis Vaccine in Adults Who Received 1 of 3 Different Primary Vaccination Schedules Tick-borne Encephalitis and Borrelial Antibodies in Serum Vaccine Study for Tick-Borne Encephalitis Virus (TBEV) Safety of and Immune Response to a Tick-Borne Encephalitis Vaccine (LGT(TP21)/DEN4) in Healthy Adults An Extension Study to Determine the Persistence of Tick-borne Encephalitis (TBE)-Specific Antibody Responses Among Children and Adolescents Previously Immunized Against TBE Tick-borne Encephalitis and Possible Borrelial Serology Cervicovaginal Immune Responses to 3 Deltoid or Thigh Intramuscular (IM) TicoVac Humoral Response to Tick-borne Encephalitis Vaccine in Elderly New Study – Humoral Response to Tick-borne Encephalitis Vaccine in Elderly Humoral and Cellular Immunity for TBE Vaccination in Allogeneic HSCT Recipients

Brief Title

Humoral and Cellular Immunity for TBE Vaccination in Allogeneic HSCT Recipients

Official Title

Characterization of Humoral and Cellular Immunity for Tick-borne Encephalitis (TBE) Vaccination in Allogeneic Blood and Marrow Graft Recipients: a Pilot Study

Brief 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.

Study Phase

Phase 2

Study Type


Primary Outcome

Outcome of the Neutralization Test (Number of Subjects With Antibody Response Measured by Neutralization Assay)

Secondary Outcome

 Antibody Response as Measured by TBE-ELISA After Second Vaccination


Tick Borne Encephalitis


TBE virus vaccine

Study Arms / Comparison Groups

 HSCT patients / TBE virus vaccine
Description:  Study population: patients who had undergone an allogeneic HSCT 11 to 13 months ago Eligible patients will receive at least two TBE vaccinations (study visit 1 - day 0, study visit 2 -1month after the first vaccination) with a total of two doses of the TBE vaccine FSME-IMMUN®. Whenever possible, the patients will receive complete primary vaccination with a third dose of TBE vaccine (study visit 9 - 9 to 12 months after the first vaccination).


* Includes publications given by the data provider as well as publications identified by National Clinical Trials Identifier (NCT ID) in Medline.

Recruitment Information

Recruitment Status


Estimated Enrollment


Start Date

July 2014

Completion Date

October 28, 2018

Primary Completion Date

October 28, 2018

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

               -  Have any acute febrile illness in the 2 weeks prior to or at the time of

               -  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)




18 Years - N/A

Accepts Healthy Volunteers

Accepts Healthy Volunteers


Christina Forstner, MD, , 

Location Countries


Location Countries


Administrative Informations



Organization ID


Responsible Party

Principal Investigator

Study Sponsor

Medical University of Vienna


 Austrian Science Fund (FWF)

Study Sponsor

Christina Forstner, MD, Principal Investigator, Medical University of Vienna

Verification Date

January 2022