Clinical trial NCT04017052: Application of a TBE-Vaccine in Obese Persons
Official title: Application of a TBE-Vaccine in Obese Persons
Study type: INTERVENTIONAL
Overall status: UNKNOWN
Phase: PHASE4
Conditions: Tick Borne Encephalitis
Lead sponsor: Medical University of Vienna
Sponsor class: OTHER
First posted: 2019-07-12
Enrollment: 73
Sex: ALL
Minimum age (years): 18
Maximum age (years): 60
Standard ages: ADULT
Accepts healthy volunteers: yes
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: PREVENTION

Brief summary: Obese people have an altered immune responsiveness. The present study investigates whether this influences immune responses to booster vaccinations (i. e. booster vaccination with TBE vaccine "FSME Immun") and if a modification of vaccination schedules is needed.

Obese adults (BMI \>30) \>18 - 60 years are compared with adults with normal weight (BMI \<25) concerning TBE-NT- antibody titers, TBE- NT antibody titer course and cellular immunity. Metabolic parameters and sexual hormones will be tested and compared as well.

Detailed description: Obese people have an altered immune responsiveness. Studies have shown that obesity has a direct effect on the immune system and leads to immunosuppression, which leads to a susceptibility to infection.We investigate whether this influences immune responses to booster vaccinations (i. e. booster vaccination with TBE vaccine "FSME Immun") and if a modification of vaccination schedules is needed.

The investigators will test and compare the humoral and cellular immune response of obese persons (BMI\>30) and persons with normal weight (BMI\<25) before and after a booster with FSME Immun.

The aim of the study is to clarify if a modification of vaccination schedules or a change of booster intervals is necessary for obese people. Furthermore this study will increase our understanding of the influence of obesity on different components of the immune system, as well as on the quality and quantity of the immune responses.

At Screening (visit 1) demographic parameters (age, gender, weight, BMI, waist/hip-ratio) will be recorded and metabolic parameters (Cholesterol, Triglycerides, HDL, LDL, Apolipoproteine, Lp(a), Glucose, Fructosamin, Leptin, Leptinreceptor on T- and B-cells (PCR), Insulin, high-sensitive CRP) and sex hormones (Testosterone, Estrogen, Progesteron, FSH, LH) will be tested. At visit 3 some metabolic parameters (Cholesterol, Triglycerides, HDL, Glucose, Fructosamin, Insulin und high-sensitive CRP) will be tested again. All parameters will be compared and correlated with humoral and cellular immune responses.

Immunglobulins: IgG, IgE, IgD, IgM, IgA will be tested at visit 1-4.

TBE antibody titers (NT) will be tested and titer course will be evaluated at visit 1-5.

At visit 1 und 2, isolation of PBMC (Peripheral Blood Mononuclear Cells) with Ficoll gradient will be carried out and the following tests will be performed:

1. Cytokine concentrations will be measured after re-stimulating the PBMC with TBE-Antigen. Duration of stimulaton: 48h; Detection with Luminex platform/ELISA: IL-2, IFNgamma, IL-10, TNF-alpha und IL-6
2. Flow cytometry: Characterization of different lymphocyte-subpopulations with antibody-panels (CD surface markers: CD19, CD3, IgD, IgM, IgG, IgA, CD10, CD27, CD127, CCR4, CD8, CD4, CD28, CD31, CD38, CCR7, CD45RA, CD25, CD24, CD38 und FOXP3).

Serious adverse events and adverse events will be recorded at all visits

All participants will be tested again at V5, performing TBE-Neutralisation-Test three years after the booster vaccination for analysis of longterm immunogenicity. Demographic parameters will be recorded again.

Participants who are not protected against TBE for another year, three years after the booster vaccination at V5 (NT \<20), will receive a booster vaccination for free.

V1 day 0, V2 day 7+3,V3 1 month +/-7 days, V4 6 months +/-14d V5 36 months+/- 1 month V6 only if TBE NT\<20

Eligibility criteria: main Inclusion Criteria:

* willingness to sign written informed consent form
* completed primary TBE immunization and at least 1 booster vaccination
* participants of both sexes between 18 and 60 years of age

main Exclusion Criteria:

* age \< 18 and \> 60 years
* BMI 25-30
* previous TBE infection
* pregnancy or breast feeding
* acute infection on day of inclusion (day 0) or at visit 5 (36 months), body temperature \> 37,9°C
* concomitant medications: systemic cortison therapy, chemotherapy, immunotherapy (allergy) immunsuppressive therapy 4 weeks prior or during the study
* administration of other vaccines 4 weeks before/after day 0
* planned surgery within 2 weeks before/after TBE booster
* any contraindication to administration of FSME-Immun® vaccine according to manufacturer's instructions
* malignant diseases within 5 years prior to the study
* autoimmune diseases
* kidney insufficiency, dialysis
* drug addiction
* plasma donor
* receipt of blood transfusions or immunoglobulins within 3 months prior to study entry / within 3 months prior to visit 5
* Severe disease with hospitalization or surgery 3 months before or during the study
* participation in a clinical trial simultaneously to visit 1-4 with receipt of vaccination and/or investigational product within one month before booster

Primary outcomes:
measure: Humoral immunity (TBE NT)
timeFrame: 1 month +/- 7 days after booster (v3)
Secondary outcomes:
measure: TBE-NT titer course
timeFrame: before booster at day 0 at all visits until 3 years after booster vaccination at V5 (36 months+/-1 month)
measure: Cellular immune response with flow cytometry
timeFrame: evaluated before (V1 day 0) and 1 week after booster vaccination (V2 day 7+3d)
measure: Measurement of Cytokines with Luminex platform/ELISA
timeFrame: evaluated before (V1 day 0) and 1 week after booster vaccination (V2 day 7+3d)
Other outcomes:
Locations:
city: Vienna
country: Austria
facility: Medical University Vienna, Institute of Specific Prophylaxis and Tropical Medicine
Study officials:
affiliation: Medical University of Vienna , ISPTM
name: Ursula Wiedermann-Schmidt, MD, PhD
role: PRINCIPAL_INVESTIGATOR
References:
citation: Garner-Spitzer E, Poellabauer EM, Wagner A, Guzek A, Zwazl I, Seidl-Friedrich C, Binder CJ, Stiasny K, Kundi M, Wiedermann U. Obesity and Sex Affect the Immune Responses to Tick-Borne Encephalitis Booster Vaccination. Front Immunol. 2020 May 27;11:860. doi: 10.3389/fimmu.2020.00860. eCollection 2020.