Clinical trial NCT01707602: Routes of Immunization and Flu Immune Responses
Official title: Impact of Immunization Routes on the Immune Response to Influenza Vaccine
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
PHASE2
Conditions: Influenza
Keywords: Intradermal
transcutaneous
influenza
routes of vaccination
T cell responses
humoral responses
skin
clinical trial
Novel application of influenza vaccine
Transcutaneous vaccination(hair follicular targeting)
Intradermal vaccination(micro-needle)
Lead sponsor: Assistance Publique - Hôpitaux de Paris
Sponsor class: OTHER
Collaborators: name: Institut National de la Santé Et de la Recherche Médicale, France
First posted: 2012-10-16
Enrollment: 60
Sex: ALL
Minimum age (years): 18
Maximum age (years): 45
Standard ages: ADULT
Accepts healthy volunteers: yes
Allocation: RANDOMIZED
Intervention model: PARALLEL

Brief summary: The project aims to evaluate the impact of skin routes of immunization (transcutaneous and intradermal vs intramuscular) on cellular and humoral responses to seasonal influenza vaccination in adults (18-45 years old).

Detailed description: New approaches addressing intradermal (ID) and transcutaneous (TC) routes of immunization have been developed over the past few years and have brought novel insight in quality and efficacy of the immune response. Indeed, compared to the muscular tissue widely used for vaccination, the skin is particularly rich in antigen presenting cells. Our recent works show that penetration of vaccine compounds into the hair follicular ducts surrounded by Langerhans cells induces potent cellular immunity in contrast to the intra-muscular immunization. Our results also suggest that differential targeting of epidermal Langerhans cells (by TC route) or dermal dendritic cells (by ID route) could modulate the intensity and quality of the immune response to vaccine.

The aim of this study is to evaluate the immune response to a seasonal influenza vaccine when administrated byTC (hair follicular targeting needle-free method), ID (micro-needle injection) and IM (conventional intramuscular injection) routes of immunization. Along with our previous pre-clinical and clinical studies, here we hypothesize that differential targeting of epidermis or dermis antigen-presenting cells will have a differential impact on the cellular and humoral immune responses to Influenza vaccine.

Objectives:

We will conduct a phase I/II clinical trials on 60 healthy volunteers to compare TC and ID routes of immunization to the conventional intramuscular (IM) vaccination. The impact of these routes on cellular and humoral immune responses to seasonal influenza vaccine will be assessed at baseline, day 21 (effector phase) and month 5 (memory phase) after vaccination.

Outcomes:

Using the seasonal Influenza vaccine as an example of conventional vaccine, this study will evaluate and compare the efficacy ofTC, ID and IMroutes of immunization to induce cellular responses at day 21 and memory responses at month 5 phases. The generation and maintenance of Flu specific and neutralizing antibodies will be measured by Haemagglutination Inhibition and microneutralization assays.Moreover, safety and tolerance to each vaccination methods will be evaluated as well as inflammation and innate immune response induced at day 1 after vaccination.

Addressing innovative skin routes of immunization, this study represents an essential step to move forward in the development of new vaccination strategies. These results will have an important impact on the amelioration of vaccine efficacy and less invasive method of immunization.

Eligibility criteria: Inclusion Criteria:

* Healthy volunteers, age between 18 and 45 years,
* BMI between 21 - 26,
* Phototype I to IV,
* Subjects able to receive vaccine administration by any of the three administration routes,
* Signature of the written informed consent,
* Affiliated to a health social security system,

Exclusion Criteria:

* Known pregnancy or positive urine pregnancy test for women of child-bearing age,
* Known infection with HIV or/and HCV or/and HBV (AgHBs+),
* Known or suspected immune dysfunction that is caused by a medical condition, or any other Cause,
* Use, within the past 3 months, of any topical and systemic treatment that would interfere with assessment and/or investigational treatment (anti-inflammatory drugs, immunosuppressors or any immune modulator agent),
* Use of any topical treatment on the injection site within the last four weeks,
* Excessive terminal hair growth on the two investigational skin areas used for the transcutaneous mode of vaccination,
* Phototype V-VI,
* Any allergy or hypersensibility to one of the components of the Investigational Product,
* Medical history of allergy or hypersensitization to any ingredient of colorant used in the transcutaneous mode of administration,
* Administration of a live vaccine(≤ 28 days) or inactivated (≤ 14 days) or planned vaccination within 3months of inclusion (D0),
* Medical history of skin cancer,
* Any acute skin affection which may interfere with the trial assessment on the injection site,
* Any acute or chronic infectious which may interfere with the trial assessment four weeks prior to enrolment,
* Prevision of UV sessions or sun exposure 6 weeks prior to the study or during the study period,
* Febrile illness(at least 37.5°Cmeasuredorally), any acute infectious event within one week prior to enrolment,
* Flu confirmed by the presence of fever≥38.5°Cassociated with respiratory symptoms
* History of GuillainBarre syndrome or brachial neuritis following a previous vaccination.
* Participation in an other biomedical research during the study period or period of exclusion when inclusion
* Subject being in the exclusion period of a previous clinical trial,

Primary outcomes:
measure: CD8 T cell responses
timeFrame: 21 days
Secondary outcomes:
measure: Safety
timeFrame: 5 months
measure: Haemagglutination Inhibition
timeFrame: 5 months
measure: CD4 T cell responses
timeFrame: 21 days
measure: Memory CD8 and CD4 T cell responses
timeFrame: 5 months
measure: Inflammation
timeFrame: 1 day
Other outcomes:
Locations:
city: PARIS Cedex 14
country: France
facility: GH Cochin - Broca - Hôtel-Dieu CIC BT505
Study officials:
affiliation: Assistance Publique - Hôpitaux de Paris
name: Odile LAUNAY, M.D. Ph. D
role: PRINCIPAL_INVESTIGATOR
References:
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citation: McMichael AJ, Ting A, Zweerink HJ, Askonas BA. HLA restriction of cell-mediated lysis of influenza virus-infected human cells. Nature. 1977 Dec 8;270(5637):524-6. doi: 10.1038/270524a0. No abstract available.
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citation: Vogt A, Mahe B, Costagliola D, Bonduelle O, Hadam S, Schaefer G, Schaefer H, Katlama C, Sterry W, Autran B, Blume-Peytavi U, Combadiere B. Transcutaneous anti-influenza vaccination promotes both CD4 and CD8 T cell immune responses in humans. J Immunol. 2008 Feb 1;180(3):1482-9. doi: 10.4049/jimmunol.180.3.1482.
citation: Mahe B, Vogt A, Liard C, Duffy D, Abadie V, Bonduelle O, Boissonnas A, Sterry W, Verrier B, Blume-Peytavi U, Combadiere B. Nanoparticle-based targeting of vaccine compounds to skin antigen-presenting cells by hair follicles and their transport in mice. J Invest Dermatol. 2009 May;129(5):1156-64. doi: 10.1038/jid.2008.356. Epub 2008 Dec 4.
citation: Liard C, Munier S, Arias M, Joulin-Giet A, Bonduelle O, Duffy D, Shattock RJ, Verrier B, Combadiere B. Targeting of HIV-p24 particle-based vaccine into differential skin layers induces distinct arms of the immune responses. Vaccine. 2011 Aug 26;29(37):6379-91. doi: 10.1016/j.vaccine.2011.04.080. Epub 2011 May 7.
citation: Liard C, Munier S, Joulin-Giet A, Bonduelle O, Hadam S, Duffy D, Vogt A, Verrier B, Combadiere B. Intradermal immunization triggers epidermal Langerhans cell mobilization required for CD8 T-cell immune responses. J Invest Dermatol. 2012 Mar;132(3 Pt 1):615-25. doi: 10.1038/jid.2011.346. Epub 2011 Dec 15.
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