Routes of Immunization and Flu Immune Responses

NCT01707602 | Completed Phase 1

• 2 other identifiers: P1202012012-001967-55
• Study Type: interventional
• Target: 60
• Locations: 1 country
• Sites: 1

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).

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)

Outcome Measures

Primary Outcomes (1)

• CD8 T cell responses

  CD8 T cell responses against the specific vaccine strain will be measured at baseline and day 21 after vaccination by flow cytometry. Secretion of cytokines measured by intracellular staining will be compared between TC, ID and IM routes of vaccination.

  21 days

Secondary Outcomes (5)

• Safety

  5 months

• Haemagglutination Inhibition

  5 months

• CD4 T cell responses

  21 days

• Memory CD8 and CD4 T cell responses

  5 months

• Inflammation

  1 day

Study Arms (3)

Arm A

EXPERIMENTAL

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

Biological: INTANZA® 15 T

Arm B

ACTIVE COMPARATOR

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

Biological: INTANZA® 15

Arm C

ACTIVE COMPARATOR

Type : Vaccine Name: Vaxigrip® Description :Intramuscular vaccination

Biological: Vaxigrip®

Interventions

INTANZA® 15 BIOLOGICAL

intradermal vaccination

Arm B

Vaxigrip® BIOLOGICAL

Intramuscular vaccination

Arm C

INTANZA® 15 T BIOLOGICAL

transcutaneous vaccination

Arm A

Eligibility Criteria

• Age: 18 Years - 45 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64)

You may qualify if:

• 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,

You may not qualify if:

• 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,
• 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

Sponsors & Collaborators

• Assistance Publique - Hôpitaux de Paris: lead
• Institut National de la Santé Et de la Recherche Médicale, France: collaborator

Study Sites (1)

GH Cochin - Broca - Hôtel-Dieu CIC BT505

Paris, 75679, France

Location

Related Publications (11)

• 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.

  PMID: 20303671 BACKGROUND

• 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.

  PMID: 593371 BACKGROUND

• 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.

  PMID: 20520820 BACKGROUND

• 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.

  PMID: 21817854 BACKGROUND

• 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.

  PMID: 18486285 BACKGROUND

• 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.

  PMID: 16614727 BACKGROUND

• 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.

  PMID: 18209043 BACKGROUND

• 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.

  PMID: 19052565 BACKGROUND

• 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.

  PMID: 21554912 BACKGROUND

• 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.

  PMID: 22170490 BACKGROUND

• 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.

  PMID: 30843873 DERIVED

MeSH Terms

Conditions

Influenza, Human

Interventions

vaxigrip

Condition Hierarchy (Ancestors)

Respiratory Tract Infections; Infections; Orthomyxoviridae Infections; RNA Virus Infections; Virus Diseases; Respiratory Tract Diseases

Study Officials

• Odile LAUNAY, M.D. Ph. D

  Assistance Publique - Hôpitaux de Paris

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: RANDOMIZED
• Masking: NONE
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: October 12, 2012
• First Posted: October 16, 2012
• Study Start: October 1, 2012
• Primary Completion: December 1, 2012
• Study Completion: April 1, 2013
• Last Updated: August 5, 2013

Record last verified: 2013-07

Locations

FR (1)