Comparison of Laser Assisted Epidermal to Intradermal Administration of Seasonal Influenza Vaccine

Study Overview
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Brief Summary
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It is the aim of the present study to compare the immunogenicity induced by a laser-assisted epidermally administered seasonal influenza vaccine to an intradermally administered seasonal influenza vaccine.

Detailed Description
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The skin is an attractive tissue for vaccination due to the impact of the cutaneous micro-environment on the adaptive and non-adaptive immune responses. Conventionally many vaccines are administered subcutaneously. Immune-competent cells however are not resident in the subcutaneous fat tissue, but instead are located in the epidermis and the dermis of the skin. Depending on the targeted skin layer and administration method, different immunological outcomes are thus anticipated following vaccination. In the present study, the immunogenicity (in terms of activation of B-cell mediated and T-cell mediated immune responses) of laser-assisted epidermally administered seasonal influenza vaccine will be compared to needle-based intradermal administration of the same seasonal influenza vaccine.

Official Title
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Safety and Immunogenicity of Laser Assisted Epidermally Administered Seasonal Influenza Vaccine in Comparison to Intradermally Administered Seasonal Influenza Vaccine

Conditions
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Influenza in Human

Intervention / Treatment
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* Biological: seasonal influenza vaccine
* Device: fractional Er:Yag laser


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Written informed consent 18-30 years old (male or female), Photo type I to IV (according to Fitzpatrick scale), Subject must be willing and able to comply with study protocol for the duration of the study, Females of childbearing potential (FCB) must maintain reliable contraception throughout the study. Exclusion Criteria: Known pregnancy or positive pregnancy test for women of child bearing potential, Positive screening assessment for human immunodeficiency virus or viral hepatitis (Hepatitis B or Hepatitis C) Known or suspected immune dysfunction that is caused by a medical condition, or any other cause and that would interfere with the conduct of the study, Use, within the past 3 months, of any topical or systemic treatment that would interfere with assessment and/or investigational treatment (anti-inflammatory drugs, immune suppressors or any immune modulator agent), Use of any topical treatment on the injection site within the last four weeks, Photo type V and VI (according to Fitzpatrick scale), Skin lesions or excessive hair growth at treatment site, Any history of seasonal influenza in the past 6 months, Any seasonal influenza vaccine in the past, Preexisting HAI antibody titers of >40 against more than one influenza strain included in the vaccine, Acute illness or febrile illness (over 37,5°C) within one week prior to enrollment, Hypersensitivity to elements of the influenza vaccine (e.g. egg), Administration of any live vaccine (< 28 days) or inactivated/toxoid vaccine (< 14 days) or planned vaccination within 3 months after inclusion, Medical history of skin cancer, History of Guillain Barre syndrome or brachial neuritis following previous vaccination, Any history of having blood transfusions or administration with gamma globulin in the past 3 months Women of childbearing potential not actively practicing birth control or using medically accepted device or therapy, Subject being judged as inadequate for following the procedures of the trial by investigator, Participation in another clinical trial (including follow up phase of a previous clinical trial)

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 30 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: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Laser assisted epidermal application<br>Laser pretreatment: 4 adjacent areas of 2 cm² each (14mm x 14 mm) will be pretreated with an Erbium Yttrium Aluminium Garnet laser (22,7 J/cm², 2 pulses, Density: 5%) generating micropores with a depth of approximately 91 µm. 0,1 ml of Intanza (15 µg, seasonal trivalent influenza vaccine) will be topically administered on the laser-treated area. | Biological: seasonal influenza vaccine<br>* influenza vaccine containing 15 µg haemagglutinin of three seasonal influenza virus strains recommended by WHO<br>* Other names: INTANZA;Device: fractional Er:Yag laser<br>* Fraction laser device to apply micorpores of defined depth and density into skin.<br>* Other names: Pantec P.L.E.A.S.E.;|
| Active Comparator: Intradermal application<br>0,1 ml of Intanza (15 µg, seasonal trivalent influenza vaccine) will be intradermally injected in the deltoid area. | Biological: seasonal influenza vaccine<br>* influenza vaccine containing 15 µg haemagglutinin of three seasonal influenza virus strains recommended by WHO<br>* Other names: INTANZA;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Haemagglutination inhibition (HAI) | HAI against each vaccine virus strain | day 1 and day 29 | 
| Frequency of vaccine specific T-cell responders | Number of subjects achieving a T-cell stimulation index of >3 | day 1, day 15 and day 29 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Seroconversion rate | Proportion of subjects achieving at least a four fold HAI titer increase against each vaccine virus strain from day 1 to day 29 | day 1 and day 29 | 
| Seroprotection rate | Proportion of subjects achieving a HAI titer of > 1:40 against each vaccine virus strain at day 29 | day 1 and day 29 | 
| Geometric Mean fold rise (GMFR) of antibody titers | GMFR of antibody titers against each vaccine virus strain from day 1 to day 29. | day 1 and day 29 | 
| Magnitude of T-cell response | Magnitude of T-cell response (SI values) against influenza vaccine on day 1, day 15 and day 29. | day 1 , day 15 and day 29 | 
| Frequency and severity of local and systemic adverse events following vaccination |  | day 1 to day 29 |