Immune Responses After a Booster Immunisation With IXIARO® in Elderly Compared to Young Individuals.

Study Overview
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Brief Summary
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The aim of this study is to investigate the immune responses following a booster immunisation with the Japanese Encephalitis vaccine in elderly subjects (above 60 years of age) in comparison to a young study group.

Detailed Description
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The condition under investigation is the naturally aging immune system. The aim of this study is to investigate the immune responses following a booster immunisation with the Japanese Encephalitis vaccine in elderly subjects (above 60 years of age) in comparison to a young study group.Testing the difference of the JEV-antibody titre increase between young and elderly adults between visit 1 (before booster vaccination) and up to visit 4 (6 months after booster vaccination). Testing cellular immunity (cytokine production after JEV as well as TBE stimulation) on visit 1, 2 (one week after booster immunisation) and 3 between both age groups. Testing of surface markers of different T and B cell subsets before and after JE-booster vaccination (on visit 1-3) in comparison between both age groups. Testing TBE-antibody titres before and after JE-booster vaccination (on visit 1-4) in both age groups. Testing CMV serology at visit 1 in both age groups.

Official Title
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Characterisation of Cellular and Humoral Immune Responses Following the First Booster Immunisation With the Inactivated, Purified Japanese Encephalitis Vaccine IXIARO® in Elderly Compared to Young Individuals.

Conditions
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Japanese Encephalitis Vaccine

Intervention / Treatment
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* Biological: IXIARO®- Japanese Encephalitis vaccine


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: participation in the preceeding study IXIARO®-senescence (EudraCTno: 2010-018630-52) without protocoll violation OR 2 documented IXIARO® vaccinations 28 days (-8/+ 30 days) apart between January 2010 and April 2014 at the age of 18 to 40 years or above the age of 60. good state of health including individuals with medically controlled minor underlying disease (such as hypertension, hypercholesterinemia, NIDDM) willingness to sign written informed consent major Exclusion Criteria: Already received an booster (3rd dose) of IXIARO ® Vaccination with other JE vaccine (e.g. Je-vax) clinically manifest infection with another Flavivirus within 1 year prior study inclusion (yellow fever, Dengue fever, West Nile, TBE) past infection with the JEV vaccination against yellow fever, Dengue, West Nile within 6 months prior to study inclusion TBE vaccination within the last 30 days prior to study inclusion immunosuppressive therapy (intake>14d) within 30 days before IXIARO booster till V3 (day 42+/-4), Corticosteroids like Prednisolon > and = 20mg/day; allowed: topic or inhalative application immunodeficiency or st. p. organ transplantation autoimmune disease except vitiligo or diseases of the thyroid gland with thyroid hormon substitution therapy immuntherapy within 2 weeks before or after Ixiaro Booster current acute infection or exacerbation of a chronic illness cancer within the last 5 years clinically significant haematological, renal, pulmonary, hepatic, neurological, cardiovascular disease which is not treated adequately within 12 weeks before Ixiaro booster known infection with HIV, Hep B and Hep C Guillain - Barré- Syndrome (GBS) - anamnestic anamnestic anaphylaxie, atopy oder severe hypersensivity against ingredients of IXIARO drug abuse/alcohol abuse pregnancy and breastfeeding plasma donation within the last 4 months receiving blood or immunglobulins within 3 months before v1 significant mental disorder

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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Accepts Healthy Volunteers

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Prevention
Allocation: Non-Randomized
Intervention Model: Parallel Assignment
Interventional Model Description: Immune Responses After a Booster Immunisation With IXIARO® in Elderly Compared to Young Individuals.
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: young individuals<br>Immune Responses After a Booster Immunisation With IXIARO®- Japanese Encephalitis vaccine | Biological: IXIARO®- Japanese Encephalitis vaccine<br>* Booster Immunisation With IXIARO®- Japanese Encephalitis vaccine<br>|
| Active Comparator: elderly individuals<br>Immune Responses After a Booster Immunisation With IXIARO®- Japanese Encephalitis vaccine | Biological: IXIARO®- Japanese Encephalitis vaccine<br>* Booster Immunisation With IXIARO®- Japanese Encephalitis vaccine<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| JEV antibody titer increase/course between visit 1 (before the booster vaccination) and Visit 3 | Testing the difference of the JEV antibodies increase between young and elderly adults between Visit 1 (before booster vaccination) and Visit 3 (day 42+/-4 after Booster vaccination) | Visit 3 day 42+/-4 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Testing the difference of the JEV antibody titer between young and elderly adults | Testing the difference of the JEV antibody titer before the booster vaccination with IXIARO® (Visite 1, day 0) till Visit 4 (day 168 +/- 14) in comparison between the age groups | Visit 1, day 0) till Visit 4 (day 168 +/- 14) | 
| Testing cellular immunity | Testing cellular immunity (cytokine production of IL-2, IFN-g, TNF-alpha, IL-6, IL-10, IL-21 after stimulation with JEV antigen) before the booster vaccination with IXIARO® (Visit 1, day 0), seven days (Visit 2, day 7 (+2) after and after 42 days (Visit 3, day 42 (+/-4)) after that in comparison between the age groups. | Visit 1, day 0), seven days after booster vaccination (Visit 2, day 7 (+2). | 
| Testing of lymphocyte populations with FACS analysis | Testing of lymphocyte populations via testing surface markers of different B and T cell subsets with FACS and bloodcount | Visit 1, day 0), seven days after booster vaccination (Visit 2, day 7 (+2) and 42 days (Visit 3, day 42 (+/-4) after booster vaccination | 
| Testing of CMV serology | Testing of CMV Seropositivity at the time of the booster vaccination with IXIARO® at Visit 1 (day 0) in both age groups | Visit 1, day 0 | 
| TBE titer increase/course | Tick borne encephalitis titer before booster vaccination with IXIARO® (Visit 1, day 0), seven days after the booster vaccination (Visit 2, day 7 (+2),and 42 days (Visit 3, day 42 (+/-4) after the booster vaccination and 6 months (Visit 4, day 168 (+/- 14) after the booster vaccination and the in comparison between age groups. | Visit 1, day 0), seven days (Visit 2, day 7 (+2), 42 days (Visit 3, day 42 (+/-4) und 6 Months (Visit 4, day 168 (+/- 14) | 
| Testing of cellular immunity-Testing of cytokine production | Testing of cellular immunity (cytokine production of IL-2, TNF-alpha, IL-6, IL-10 after stimulation mit TBE Antigen) before and seven days after the booster vaccination with IXIARO® (Visit 1, day 0; Visit 2, day 7 (+2) in comparison between the age groups | Visit 1, day 0; Visit 2, day 7 (+2) | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Japanese Encephalitis vaccine, immune responses