Immune Response to Yellow Fever Vaccination in Adults With Atopic Dermatitis

Study Overview
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Brief Summary
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The main objective of the Atopic Dermatitis and Vaccinia Immunization Network (ADVN) is to reduce the risk of the fatal reaction, eczema vaccinatum (EV), to the smallpox vaccination in those with atopic dermatitis (AD). Since vaccination with live vaccinia virus (VV) in individuals with AD increases the risk of EV, a yellow fever vaccine was chosen. The purpose of this study is to determine the immune response to a yellow fever vaccine in adults with AD.

Detailed Description
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AD is a chronic inflammatory skin disorder characterized by recurrent viral skin infections. The purpose of this study is to understand the immune response to a yellow fever vaccine in adults with AD. This study will provide substantial information about normal and defective cutaneous immunity in participants with AD in response to a live virus vaccine, which is critical for understanding the EV reaction. An individual's participation in the study will last up to 13 weeks. Participants will be randomized into one of two arms. The first experimental arm will consist of 20 adults with AD and 20 healthy adults. They will receive one dose of YFV-17D by subcutaneous administration in the right deltoid and receive one dose of YFV-17D placebo by transcutaneous administration in the left deltoid. The second arm will consist of 20 adults with AD and 20 healthy adults. They will receive one dose of YFV-17D placebo by subcutaneous administration in the right deltoid and receive one dose of YFV-17D vaccine transcutaneously in the left deltoid. This study will consist of 6 follow-up visits over a 35 day period after study entry.

Official Title
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A Study of the Systemic and Cutaneous Immune Responses to Yellow Fever Vaccination in Atopic Dermatitis Subjects

Conditions
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Atopic Dermatitis

Intervention / Treatment
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* Biological: Live Yellow Fever Vaccine (YFV-17D)
* Drug: YFV-17D Placebo


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Diagnosis of Atopic Dermatitis or Non-atopic control Born and currently residing in the United States Weight of at least 110 lbs at the Screening Visit Not previously vaccinated for YFV, tick-borne encephalitis (TBEV), Japanese encephalitis virus (JEV), or dengue fever Agree to use adequate contraception 30 days prior to and until their participation in the study is completed. More information on this criterion can be found in the protocol. Exclusion Criteria: AD subjects with exfoliative erythroderma or lacking a minimum 10 cm diameter area of normal appearing skin on the deltoid or thigh vaccination sites Have a body mass index (BMI) of 30 or greater at the Screening Visit Known history of infection with YFV, dengue fever, TBEV, JEV, or West Nile Virus (WNV) A family history of severe reactions to the yellow fever vaccine Traveled to Africa or South America (including participants who plan to travel to these areas prior to completion of the study) History of egg allergy or have a positive egg allergy skin prick test that is administered at the Screening visit History of acute hypersensitivity reaction to any components of the yellow fever vaccine (including gelatin) Have latex allergy Have lidocaine allergy Are allergic or hypersensitive to TegadermTM Received systemic immunosuppressants within 30 days prior to receiving the vaccination Received systemic corticosteroids, anti inflammatory biologics (e.g., alefacept, etanercept, etc.), or calcineurin inhibitors within 30 days prior to receiving the vaccination Received systemic antibiotics or antivirals within 7 days of receiving the vaccination Received greater than 440 mcg of inhaled steroids per day within 6 months prior to receiving the vaccination Received Xolair (Omalizumab) within 1 year prior to receiving the vaccination Received immunotherapy within 30 days prior to receiving the vaccination Received any vaccine within 30 days prior to randomization or expected receipt 30 days after randomization Received topical antibiotics, antivirals, immune enhancers (e.g., imiquimod), or calcineurin inhibitors within 7 days prior to receiving the vaccination Received topical corticosteroids within 7 days prior to receiving the vaccination Received phototherapy (e.g., ultraviolet light B [UVB], psoralen plus ultraviolet light A [PUVA]) within 30 days prior to receiving the vaccination Acute febrile illness or active fungal, bacterial, or viral infections (subjects may be reconsidered for enrollment once the condition has resolved) Skin disease other than AD that might compromise the stratum corneum barrier (e.g., clinically evident ichthyosis, bullous disease, psoriasis) Current or past history of malignancy or of autoimmune or immunodeficiency diseases. More information on this criterion can be found in the protocol. Pregnant or breastfeeding Have an anti-nuclear antibody (ANA) titer that is equal to or greater than 1/160 at the Screening Visit Have a serum immunoglobulin (Ig)G, IgM, IgA, C3, or C4 level below the normal range at the Screening Visit Have a manual lymphocyte count that is less than 1000 lymphocytes per microliter

Ages Eligible for Study
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Minimum Age: 27 Years
Maximum Age: 43 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: Basic Science
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: YFV-17D (Right Deltoid)<br>Participants will be randomized within each atopic dermatitis (AD) severity subgroup or as non-atopic controls to either subcutaneous (SC) or transcutaneous (TC) vaccine administration. In this arm, participants will receive a standard vaccine dose (5.5x10^4 Plaque Forming Units) of YFV-17D administered subcutaneously in the right deltoid and placebo vaccination transcutaneously (then covered with a semi-occlusive dressing) in the left deltoid. The site pharmacist will maintain the blind and an unblinded (i.e., masked) site coordinator will administer assigned treatment: investigators, participants and assessors remain blinded to treatment assignments throughout the duration of the trial. | Biological: Live Yellow Fever Vaccine (YFV-17D)<br> <br> Drug: YFV-17D Placebo<br> <br> |
| Experimental: YFV-17D (Left Deltoid)<br>Participants will be randomized within each atopic dermatitis (AD) severity subgroup or as non-atopic controls to either subcutaneous (SC) or transcutaneous (TC) vaccination. In this arm, participants will receive YFV-17D vaccination (1x10^3 Plaque Forming Units) by transcutaneous administration (then covered with a semi-occlusive dressing to optimize YFV-17D absorption) in the left deltoid and placebo by subcutaneous administration in the right deltoid. The site pharmacist will maintain the blind and an unblinded (i.e., masked) site coordinator will administered treatment: investigators, participants and assessors remain blinded to treatment assignments throughout the duration of the trial. | Biological: Live Yellow Fever Vaccine (YFV-17D)<br> <br> Drug: YFV-17D Placebo<br> <br> |

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Comparison of Anti-YF Antibody Levels by Measurement of Log10 Neutralization Index (LNI): YFV-17D TC- (AD) Participants Compared to YFV-17D TC- (Non-AD) Participants | Log10 Neutralization Index (LNI) is the Log10 difference in virus titer (measurement of amount of virus) between pre-vaccination and post-vaccination. An LNI greater than or equal to 0.7 suggests that a person has active immunity against Yellow Fever virus. | 30 days after Yellow Fever (YF) immunization (Acceptable Blood Draw Range: Day 28 - Day 35 after YF immunization) | 
| Comparison of Anti-YF Antibody Levels by Measurement of Log10 Neutralization Index (LNI): YFV-17D SC - (AD) Participants Compared to YFV-17D SC- (Non-AD) Participants | Log10 Neutralization Index (LNI) is the Log10 difference in virus titer (measurement of amount of virus) between pre-vaccination and post-vaccination. An LNI greater than or equal to 0.7 suggests that a person has active immunity against Yellow Fever virus. | 30 days after YF immunization (Acceptable Blood Draw Range: Day 28 - Day 35 after Yellow Fever immunization) | 
| Comparison of Anti-YF Antibody Levels by Measurement of Log10 Neutralizing Titer 50 (NT50): YFV-17D TC - (AD) Participants Compared to YFV-17D TC - (Non - AD) Participants | Neutralization titer (NT50) is the dilution of serum (antibody) that results in a 50% reduction in the amount of virus. A higher NT50 number reflects the presence of more protective antibody levels against the Yellow Fever virus. Some studies have used an NT50 titer of 1:10 or 1:20 as the minimum level to suggest that a person has active immunity against the Yellow Fever virus. | 30 days after Yellow Fever (YF) immunization (Acceptable Blood Draw Range: Day 28 - Day 35 after YF immunization) | 
| Comparison of Anti-YF Antibody Levels by Measurement of Log10 Neutralizing Titer 50 (NT50): YFV-17D SC - (AD) Participants Compared to YFV-17D SC - (Non-AD) Participants | Neutralization titer (NT50) is the dilution of serum (antibody) that results in a 50% reduction in the amount of virus. A higher NT50 number reflects the presence of more protective antibody levels against the Yellow Fever virus. Some studies have used an NT50 titer of 1:10 or 1:20 as the minimum level to suggest that a person has active immunity against the Yellow Fever virus. | 30 days after Yellow Fever (YF) immunization (Acceptable Blood Draw Range: Day 28 - Day 35 after YF immunization) | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Comparison of Count of Seroconverters: YFV-17D TC- (AD) Participants Compared to YFV-17D TC - (Non-AD) Participants | Seroconversion is defined as a Log10 Neutralization Index (LNI) of 0.7 or higher. A value greater than or equal to 0.7 suggests that a person has active immunity against Yellow Fever virus. | Day 0 to Day 30 (Acceptable Post-Vaccination Blood Draw Range: Day 28 - Day 35) | 
| Comparison of Count of Seroconverters: YFV-17D SC - (AD) Participants Compared to YFV-17D SC - (Non-AD) Participants | Seroconversion is defined as a Log10 Neutralization Index (LNI) of 0.7 or higher. A value greater than or equal to 0.7 suggests that a person has active immunity against Yellow Fever virus. | Day 0 to Day 30 (Acceptable Post-Vaccination Blood Draw Range: Day 28 - Day 35) | 
| Comparison in Log10 Transformed Lymphocyte Count on Day 30 Post YF Immunization: IFN-gamma Positive, Tumor Necrosis Factor- Alpha (TNF Alpha) Positive, CD4 Positive T-cells, YFV-17D SC - (AD) Compared to YFV-17D SC - (Non- AD) Participants | Comparison by designated reporting groups: the Log10 transformed lymphocyte count of CD4 Positive T-cells expressing IFN-gamma and TNF-alpha in every 10^6 CD4 Positive T-cells on Day 30 (acceptable blood draw window: Day 28 - 35). | Day 30 (Day 28-35) | 
| Comparison in Log10 Transformed Lymphocyte Count on Day 30 Post YF Immunization: IFN-gamma Positive, Tumor Necrosis Factor- Alpha (TNF Alpha) Positive , CD4 Positive T-cells, YFV-17D TC - (AD) Compared to YFV-17D TC - (Non-AD) Participants | Comparison by designated reporting groups: the Log10 transformed count of CD4 Positive T-cells that express IFN-gamma and TNF-alpha in every 10^6 CD4 Positive T- Cells (Day 30). A higher count reflects a better immune response to Yellow Fever virus. | Day 30 (Day 28-35) | 
| Comparison in Log10 Transformed Lymphocyte Count on Day 30 Post YF Immunization: IFN-gamma Positive, Tumor Necrosis Factor- Alpha (TNF Alpha) Positive, CD8 Positive T-cells, YFV-17D SC -(AD) Compared to YFV-17D SC - (Non-AD) Participants | Comparison by designated reporting groups: the Log10 transformed lymphocyte count of CD8 Positive T-cells expressing IFN-gamma and TNF-alpha in every 10^6 CD8 Positive T-cells. | Day 30 (Day 28-35) | 
| Comparison in Log10 Transformed Lymphocyte Count on Day 30 Post YF Immunization: IFN-gamma Positive, Tumor Necrosis Factor- Alpha (TNF Alpha) Positive, CD8 Positive T-cells, YFV-17D TC - (AD) Compared to YFV-17D TC - (Non-AD) Participants | Comparison by designated reporting groups: the Log10 transformed count of CD8 Positive T-cells expressing IFN-gamma and TNF-alpha in every 10^6 CD8 Positive T-cells. | Day 30 (Day 28-35) | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Yellow Fever Vaccine, Scarification Method, Atopic Dermatitis, IgG antibodies