Influence of Persistent CMV-infection on Immune Senescence

Study Overview
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Brief Summary
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Recent studies indicate that persistent viral infections particularly with Cytomegalovirus (CMV) might have a negative impact on immune senescence (i.e. immunocompetence of elderly individuals). We will test this hypothesis by performing a vaccination trial in healthy elderly individuals subdivided in two groups of CMV-seropositive and CMV-seronegative individuals. All individuals will be vaccinated with the currently licensed vaccine for the prevention of TBE (FSME Immun CC) which is recommended for the general population in our area. Vaccination efficacy will be monitored longitudinally concerning the TBEV-specific antibody (TBEV-neutralization, TBEV-specific ELISA) and T cell response (ELISpot, cytokine production). Vaccination efficacy will be compared between CMV+ and CMV- individuals and correlated with the CMV-specific immune response in CMV+ individuals.

Official Title
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Influence of Persistent CMV-infection on Immune Senescence Evaluated With a Prospective Vaccination Trial Against Tick-borne Encephalitis Virus in Healthy Elderly Individuals (CYTEL-Study)

Conditions
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Immune Senescence

Intervention / Treatment
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* Biological: Vaccination against TBEV (FSME Immun CC)


Participation Criteria
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Eligibility Criteria
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Inclusion criteria: Age > 70 years Healthy according to a health questionnaire (completed before screening) TBE-Vaccination indicated (exposure to TBEV-infested ticks possible) Capable to make an informed decision and to understand the informed consent form Informed consent signed by patient and study physician Exclusion criteria: Previous exposure to TBEV (natural or vaccination) Immunodeficiency, history of autoimmune disease or current intake of immune-modulating drugs (corticosteroids a.s.o.) Persistent (> 3 months) pharmacological treatment with more than one drug of relevance (exception: combination antihypertensives) Contraindication for TBEV-vaccination Condition that would drastically interfere with clinic attendance and/or adherence to the protocol Past medical history or current treatment for one of the following conditions: Chronic cardiac disease (Coronary heart disease, heart failure), chronic pulmonary disease (COPD), chronic kidney disease, diabetes mellitus, previous stroke, epilepsy, Parkinsons disease, dementia Hemoglobin <12 g/l Random plasma glucose (RPG) > 11.1 mmol/l OR fasting plasma glucose (FPG) > 6.9 mmol/l (FPG required, if RPG is 7.0-11.0 mmol/l) Calculated Creatinin-Clearance < 50 ml/min TBEV-serology positive

Ages Eligible for Study
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Minimum Age: 70 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

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: Single Group Assignment
Masking: Single


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Other: CMV-seropositive<br>Cytomegalovirus-seropositive individuals at screening (week 0). Intervention: Intervention: Vaccination against tick-borne encephalitis by intramuscular injection into the left (or right) deltoid muscle of 0.5 ml FSME Immun CC for adults (2.4 ug of formalin inactivated TBEV antigen) at time point 0, after 4 weeks and after 24 weeks. | Biological: Vaccination against TBEV (FSME Immun CC)<br>* Intramuscular injection into the left (or right) deltoid muscle of 0.5 ml FSME Immun CC for adults (2.4 ug of formalin inactivated TBEV antigen) at time point 0, after 4 weeks and after 24 weeks.<br>|
| Other: CMV-seronegative<br>Cytomegalovirus-seronegative individuals at screening (week 0). Intervention: Vaccination against tick-borne encephalitis by intramuscular injection into the left (or right) deltoid muscle of 0.5 ml FSME Immun CC for adults (2.4 ug of formalin inactivated TBEV antigen) at time point 0, after 4 weeks and after 24 weeks. | Biological: Vaccination against TBEV (FSME Immun CC)<br>* Intramuscular injection into the left (or right) deltoid muscle of 0.5 ml FSME Immun CC for adults (2.4 ug of formalin inactivated TBEV antigen) at time point 0, after 4 weeks and after 24 weeks.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Geometric mean titer (GMT) of anti-TBEV-antibodies measured by TBEV-neutralisation assay and ELISA one month after each TBEV-vaccine administration in the group of CMV-seropositive versus CMV-seronegative individuals |  | One month after each TBEV-vaccine administration | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Efficacy of TBEV-vaccination in healthy elderly individuals (Geometric mean antibody titer measured by TBEV-neutralisation test). |  | One month after 3rd TBEV-vaccine administration | 
| Safety of TBEV-vaccination in healthy elderly individuals. |  | One month after 3rd TBEV-vaccine administration. | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Cytomegalovirus (CMV), Tick-borne encephalitis virus (TBEV), Ageing, Vaccine, Immunity