Routes of Immunization and Flu Immune Responses

NCT ID: NCT01707602

Last Updated: 2013-08-05

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE1/PHASE2
• Total Enrollment: 60 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2012-10-31
• Study Completion Date: 2013-04-30

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.

Conditions

Influenza

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Blinding Strategy: NONE

Study Groups

Arm A

Type Vaccine Name: INTANZA® 15 T Description : transcutaneous vaccination

Group Type: EXPERIMENTAL

INTANZA® 15 T

Intervention Type: BIOLOGICAL

transcutaneous vaccination

Arm B

Type: Vaccine Name: INTANZA® 15ug Description : intradermal vaccination

Group Type: ACTIVE_COMPARATOR

INTANZA® 15

Intervention Type: BIOLOGICAL

intradermal vaccination

Arm C

Type : Vaccine Name: Vaxigrip® Description :Intramuscular vaccination

Group Type: ACTIVE_COMPARATOR

Vaxigrip®

Intervention Type: BIOLOGICAL

Intramuscular vaccination

Interventions

INTANZA® 15

intradermal vaccination

Intervention Type: BIOLOGICAL

Vaxigrip®

Intramuscular vaccination

Intervention Type: BIOLOGICAL

INTANZA® 15 T

transcutaneous vaccination

Intervention Type: BIOLOGICAL

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,

• Minimum Eligible Age: 18 Years
• Maximum Eligible Age: 45 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: Yes

Sponsors

Institut National de la Santé Et de la Recherche Médicale, France

OTHER_GOV

Sponsor Role: collaborator

Assistance Publique - Hôpitaux de Paris

OTHER

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Odile LAUNAY, M.D. Ph. D

Role: PRINCIPAL_INVESTIGATOR

Assistance Publique - Hôpitaux de Paris

Locations

GH Cochin - Broca - Hôtel-Dieu CIC BT505

Paris, , France

Countries

France

References

Combadiere B, Siberil S, Duffy D. Keeping the memory of influenza viruses. Pathol Biol (Paris). 2010 Apr;58(2):e79-86. doi: 10.1016/j.patbio.2010.01.010. Epub 2010 Mar 19.

Reference Type: BACKGROUND

PMID: 20303671 (View on PubMed)

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.

Reference Type: BACKGROUND

PMID: 593371 (View on PubMed)

Combadiere B, Vogt A, Mahe B, Costagliola D, Hadam S, Bonduelle O, Sterry W, Staszewski S, Schaefer H, van der Werf S, Katlama C, Autran B, Blume-Peytavi U. Preferential amplification of CD8 effector-T cells after transcutaneous application of an inactivated influenza vaccine: a randomized phase I trial. PLoS One. 2010 May 26;5(5):e10818. doi: 10.1371/journal.pone.0010818.

Reference Type: BACKGROUND

PMID: 20520820 (View on PubMed)

Combadiere B, Liard C. Transcutaneous and intradermal vaccination. Hum Vaccin. 2011 Aug;7(8):811-27. doi: 10.4161/hv.7.8.16274. Epub 2011 Aug 1.

Reference Type: BACKGROUND

PMID: 21817854 (View on PubMed)

Lambert PH, Laurent PE. Intradermal vaccine delivery: will new delivery systems transform vaccine administration? Vaccine. 2008 Jun 19;26(26):3197-208. doi: 10.1016/j.vaccine.2008.03.095. Epub 2008 Apr 22.

Reference Type: BACKGROUND

PMID: 18486285 (View on PubMed)

Vogt A, Combadiere B, Hadam S, Stieler KM, Lademann J, Schaefer H, Autran B, Sterry W, Blume-Peytavi U. 40 nm, but not 750 or 1,500 nm, nanoparticles enter epidermal CD1a+ cells after transcutaneous application on human skin. J Invest Dermatol. 2006 Jun;126(6):1316-22. doi: 10.1038/sj.jid.5700226.

Reference Type: BACKGROUND

PMID: 16614727 (View on PubMed)

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.

Reference Type: BACKGROUND

PMID: 18209043 (View on PubMed)

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.

Reference Type: BACKGROUND

PMID: 19052565 (View on PubMed)

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.

Reference Type: BACKGROUND

PMID: 21554912 (View on PubMed)

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.

Reference Type: BACKGROUND

PMID: 22170490 (View on PubMed)

Goncalves E, Bonduelle O, Soria A, Loulergue P, Rousseau A, Cachanado M, Bonnabau H, Thiebaut R, Tchitchek N, Behillil S, van der Werf S, Vogt A, Simon T, Launay O, Combadiere B. Innate gene signature distinguishes humoral versus cytotoxic responses to influenza vaccination. J Clin Invest. 2019 Mar 7;129(5):1960-1971. doi: 10.1172/JCI125372. Print 2019 May 1.

Reference Type: DERIVED

PMID: 30843873 (View on PubMed)

Other Identifiers

2012-001967-55

Identifier Type: EUDRACT_NUMBER

Identifier Source: secondary_id

P120201

Identifier Type: -

Identifier Source: org_study_id