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NCT Number: NCT01991067

Humoral and Cellular Immunity for TBE Vaccination in Allogeneic HSCT Recipients

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.

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Key information

Conditions

Tick Borne Encephalitis Arbovirus Infections Brain Diseases Central Nervous System Diseases Central Nervous System Infections Central Nervous System Viral Diseases Encephalitis Encephalitis, Arbovirus Encephalitis, Tick-Borne Encephalitis, Viral Flaviviridae Infections Flavivirus Infections Infections Infectious Encephalitis Nervous System Diseases Neuroinflammatory Diseases RNA Virus Infections Tick-Borne Diseases Vector Borne Diseases Virus Diseases

Age range

18 year and older

Sex eligibility

All sexes

Study type

Interventional

Phase

Phase 2

Primary location

Medical University of Vienna, Department of Medicine I, Division of Infectious Diseases and Tropical Medicine

Vienna, 1090, Austria

Who can participate

Healthy volunteers accepted: Yes

Only the study team can determine whether someone qualifies for participation.

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)

Treatment and study plan

TBE virus vaccine

Biological

TBE virus vaccine FSME Immun is used in both arms for the study population and the control group

Other names: FSME Immun

Primary outcomes

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

    Time frame: four weeks after the second vaccination

    The Primary endpoint of this study was the antibody Response after TBE-vaccination as measured by neutralization assay four weeks after second vaccination. Antibody response was defined as a Composite endpoint by a NT-titer of >=10, and at least a two-fold increase from baseline (or titer above the highest level of measurement

Secondary outcomes

  1. Antibody Response as Measured by TBE-ELISA After Second Vaccination

    Time frame: comparison between baseline and four weeks after second vaccination

    The antibody response after TBE-vaccination four weeks after second vaccination was measured by ELISA defined by a ELISA titer of >=220 Vienna Units and at least a two-fold increase of titer from baseline

  2. Change of Antibody Concentration of NT Titer

    Time frame: between baseline and four weeks after the third vaccination

    Geometric mean fold change of NT titer between baseline and four weeks after third vaccination was compared between HSCT patients and healthy controls

  3. Lymphocyte Proliferation as a Measure of Cellular Immune Response in the Study Population Versus the Control Group Prior Vaccination

    Time frame: before vaccination

    Baseline data for lymphocyte proliferation was detected by thymidine incorporation assay after stimulation with albumin-free TBE Antigen. Data was standardized based on unstimulated controls of each participant. The stimulation index is given. The stimulation index is the ratio of the number of proliferating lymphocytes with thymidine incorporation in the presence of antigen to that in absence of antigen. A SI value equal or greater to 3.0 represents relevant lymphocyte proliferation, whereas a SI value <3.0 represents no relevant lymphocyte proliferation.

  4. Fold Induction in IL13 Cytokine Levels Before Vaccination (Baseline) in the Study Population Versus the Control Group

    Time frame: before vaccination

    Determination of secreted IL13 cytokine levels iwas performed using the Luminex System at baseline. Data was standardized based on unstimulated controls of each patient. The fold induction in the presence of TBE antigen to that in absence is given.

  5. Lymphocyte Proliferation as a Measure of Cellular Immune Response in The Study Population Versus the Control Group After Second Vaccination

    Time frame: 7 days after second vaccination

    Data for lymphocyte proliferation was detected by thymidine incorporation assay after stimulation with albumin-free TBE antigen 7 days after the second vaccination. Data was standardized based on unstimulated controls of each participant. The stimulation index is given. The stimulation index is the ratio of the number of proliferating lymphocytes with thymidine incorporation in the presence of antigen to that in absence of antigen. A SI value equal or greater to 3.0 represents relevant lymphocyte proliferation, whereas a SI value <3.0 represents no relevant lymphocyte proliferation.

  6. Lymphocyte Proliferation as a Measure of Celluar Immune Response in the Study Population Versus the Control Group After Third Vaccination

    Time frame: 7 days after Third Vaccination

    Data for lymphocyte proliferation was detected by thymidine incorporation assay after stimulation with albumin-free TBE antigen 7 days after the third vaccination. Data was standardized based on unstimulated controls of each participant. The stimulation index is given. The stimulation index is the ratio of the number of proliferating lymphocytes with thymidine incorporation in the presence of antigen to that in absence of antigen. A SI value equal or greater to 3.0 represents relevant lymphocyte proliferation, whereas a SI value <3.0 represents no relevant lymphocyte proliferation.

  7. Fold Induction in IL13 Cytokine Levels in the Study Population Versus the Control Group After Second Vaccination

    Time frame: 7 days after second vaccination

    Determination of secreted IL13 cytokine levels was performed using the Luminex System 7 days after second vaccination. Data was standardized based on unstimulated controls of each patient. The fold induction in the presence of TBE antigen to that in absence is given.

  8. Fold Induction in IL13 Cytokine Levels in the Study Population Versus the Control Group After Third Vaccination

    Time frame: 7 days after third vaccination

    Determination of secreted IL13 cytokine levels was performed using the Luminex System 7 days after third vaccination. Data was standardized based on unstimulated controls of each patient. The fold induction in the presence of TBE antigen to that in absence is given.

Sponsors and collaborators

Lead sponsor

Medical University of Vienna

Other

Collaborators

  • Austrian Science Fund (FWF)

Registry information

Official study title

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

Important dates

Study start
2014
Primary completion
2018
Study completion
2018
First posted
Nov 25, 2013
Registry last updated
Feb 3, 2022

OpenTrials presents study information sourced from ClinicalTrials.gov. The official registry record should be consulted for the latest information.

View the official ClinicalTrials.gov record (opens in a new tab)

This listing is for discovery and informational purposes only. It is not medical advice, does not guarantee that a study is recruiting, and does not determine eligibility. Contact the study team and a qualified healthcare professional when considering participation.

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