Role of Antimicrobial Peptides in Host Defense Against Vaccinia Virus

Study Overview
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Brief Summary
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Atopic dermatitis (AD) is a chronic inflammatory skin disorder characterized by recurrent viral skin infections. Recent studies have demonstrated that the skin of people with AD my have decreased antimicrobial peptide (AMP) expression. The purpose of this study is to compare smallpox virus replication and the number of AMPs and other antiviral molecules in people with AD, as compared to those seen in people with psoriasis or asthma, or healthy individuals.

Detailed Description
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AD is a chronic inflammatory skin disease characterized by frequent viral skin infections. Recent studies have found that components in the skin of people with AD may block AMP expression. AMPs are responsible for preventing infection from viruses. The purpose of this study is to examine smallpox virus replication and AMP expression in the skin of patients with AD as well as identify other antiviral molecules involved in immune response. These findings will be compared with those of people with psoriasis or asthma, or healthy individuals. This study will consist of one study visit at which skin and blood samples will be taken.

Official Title
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Role of Antimicrobial Peptides in Host Defense Against Vaccinia Virus (ADVN AMP01)

Conditions
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Atopic Dermatitis

Participation Criteria
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Eligibility Criteria
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Inclusion Criteria for Participants With AD: 2 years of age or older History of active or inactive AD OR eczema herpeticum, as defined by the ADVN standardized diagnostic criteria Parent or guardian willing to provide informed consent, if applicable Male or female of any race and ethnicity Inclusion Criteria for Participants With Asthma or Psoriasis, and for non-atopic controls: 18 years or older History of psoriasis OR history of asthma not requiring systemic medications Parent or guardian willing to provide informed consent, if applicable Male or female of any race and ethnicity Exclusion Criteria: Oral corticosteroids or any systemic immunosuppressive or immunomodulatory medication within 28 days prior to study entry Immunotherapy within 3 months prior to study entry History of bleeding disorder Aspirin, oral antihistamines, oral antibiotics, oral cyclosporine, or topical medications within 7 days of screening visit including, but not restricted to, Protopic, Elidel, topical corticosteroids, and topical antibiotics Anxiolytic agents and antidepressants within 2 days of screening visit Diabetic requiring medication Autoimmune or immunodeficiency Active fungal, bacterial, or viral infections within 7 days prior to study entry Active systemic cancer. Participants with uncomplicated nonmelanoma skin cancer are not excluded. Theophylline or leukotriene antagonists within 24 hours of screening visit Received any vaccination within 30 days prior to study entry Known lidocaine allergy Previously vaccinated for smallpox Pregnant or breastfeeding

Ages Eligible for Study
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Minimum Age: 2 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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Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Atopic Dermatitis (AD)<br>Pediatric and adult subjects who fulfill the criteria for AD, a chronic inflammatory skin disease. | |
| Inactive Atopic Dermatitis (AD)<br>Adult subjects with a prior history of active AD that has been quiescent for at least 1 year. | |
| Psoriatics<br>Adult subjects who fulfill the criteria for plaque psoriasis, a chronic inflammatory skin disease. | |
| Asthmatics (without a history of AD)<br>Adult subjects who fulfill the criteria for asthma (reactive airway disease) and have a negative history of skin disease. | |
| Eczema Herpeticum (EH<br>Pediatric and adult AD subjects with a history of EH. | |
| Healthy Volunteers<br>Healthy individuals with no history of skin or respiratory disease. | |

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Expression of vaccinia virus mRNA in non-lesional skin following inoculation with untreated vaccinia virus will be evaluated using real-time RT-PCR (Reverse transcription polymerase chain reaction). |  | 5 years | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Expression of cytokines, AMPs, other antiviral molecules, or epidermal differentiation proteins in non-lesional skin prior to and after inoculation with vaccinia virus will be evaluated using real-time RT-PCR. |  | 5 years | 
| Keratinocytes will be stimulated with vaccinia virus in the presence and absence of Th1 or Th2 cytokines. Non-lesional AD skin will be stimulated with vaccinia virus in the presence of antibodies that neutralize Th2 cytokines. |  | 5 years | 
| Vaccinia virus replication will be evaluated using a standard viral plaque assay in BS-C-1 cells and by analyzing vaccinia virus mRNA expression using real-time RT-PCR in keratinocytes and BS-C-1 cells. |  | 5 years | 
| Expression of over 20,000 genes will be evaluated by GeneChip microarrays in non-lesional skin, and PBMCs stimulated with vaccinia virus. Real-time RT-PCR of skin and PBMC will be used to confirm gene alterations found in GeneChip microarrays. |  | 5 years | 
| Ability of structural analogues of CSAs (Cyclosporine) to kill purified vaccinia virus as well as keratinocytes infected with vaccinia virus in vitro. |  | 5 years |