Safety Study Comparing a Vaccine Transcutaneous Administration to the Intramuscular Route
Condition: Healthy Volunteers; HIV Infection
MeSH terms: HIV Infections
Study type: Interventional
Phase: Phase 1

Summary: 
      The rationale for transcutaneous vaccination is based on the unique ability of cutaneous
      immune cells, especially Langerhans cells (LCs), to present antigens to the immune system.
      DCs can be found at high densities in the epidermis and the dermis of human skin, a fraction
      of which are the epidermal LCs. It is known that strong and efficient immune responses can be
      induced by targeting vaccines to skin APCs (Glenn 2003, Partidos 2003), e.g. by epicutaneous
      application of smallpox vaccine on scarified skin. Several obstacles however prevent vaccines
      from attaining sufficiently high and free concentrations in these target skin DCs.

      In this clinical trial we aim at testing the safety and immunogenicity of this new
      transcutaneous route of vaccine administration, first with a licensed, well-known, safe and
      highly immunogenic vaccine i.e. Tetagrip® vaccine, which is licensed for subcutaneous (s.c.)
      and intra-muscular routes (i.m), and to compare the induced vaccine-specific immune responses
      to those induced with the conventional (i.m) injection. We hypothesize that the
      transcutaneous application of Tetagrip® in the commercially available standard preparation of
      0.5 ml should be capable to induce at least similar antibody and CD4 and/or CD8 T cell
      responses to both the tetanus and the flu vaccinal antigens.

      This Phase I, open label, randomized study is designed to evaluate and to compare the safety
      and immunogenicity of a transcutaneous mode of Tetanus / Influenza vaccination to the
      conventional i.m. route of vaccine administration in two cohorts: The cohort I constituted of
      healthy volunteers and the cohort II of HIV-infected patients in whom the virus is stably
      controlled by antiretroviral therapy, ensuring an immune competence and a capacity to respond
      to vaccines.
    

Detailed description: 
      The proposed study aims to translate our current knowledge about vaccinology, immunology of
      the skin and on transcutaneous penetration of epicutaneously applied active compounds, into
      the development of more efficient and well tolerated vaccines, and to progress toward an
      easy-to-apply patch system for transcutaneous application of vaccines.

      To that purpose we aim at testing the safety and immunogenicity of a new transcutaneous route
      of vaccine administration. We propose to test this new route first with a well-known, safe
      and highly immunogenic vaccine i.e. anti-influenza and tetanus vaccine which is licensed for
      sub-cutaneous and intra-muscular routes, and to compare the vaccine-specific immune responses
      induced after transcutaneous administration to the conventional intramuscular (i.m)
      injection. Seasonal vaccination against influenza is recommended for all individuals at risk
      for severe flu, including persons above 60 years of age or suffering from chronic diseases
      and for medical personal. It is also highly recommended at any age to prevent influenza. In
      addition vaccination against tetanus is mandatory in childhood and requires recall injections
      every 5 years to protect against the lethal disease caused by the tetanus toxin.

      We hypothesize that the transcutaneous application of a licensed anti-influenza-tetanus
      vaccine in the commercially available standard preparation of 0.5 ml should be capable to
      induce at least similar antibody and CD4 and/or CD8 T cell responses to both the tetanus and
      the flu vaccinal antigens.

      Tetagrip® vaccine is an approved and commercially available vaccine manufactured by
      Sanofi-Pasteur, administered in one injection for preventive vaccination of adults against
      tetanus and influenza. The Tetagrip® vaccine therefore represents a safe and approved test
      vaccine to evaluate safety and immunogenicity of the mode of administration under
      investigation.

      The long term goal of this strategy is to improve the efficacy of vaccines that are currently
      encountering major obstacles such as the HIV vaccines, and to develop a non invasive mode of
      vaccine administration. Results from this study will help establish a standardized study
      protocol for the application of HIV-vaccines in future clinical trials.

      STUDY DESIGN This Phase I, open label, randomized on the vaccine administration route study
      is designed to evaluate and to compare the safety and immunogenicity of a transcutaneous mode
      of Tetanus / Influenza vaccination to the conventional i.m. route of vaccine administration
      in two cohorts: The cohort I constituted of healthy volunteers and the cohort II of
      HIV-infected patients in whom the virus is stably controlled by antiretroviral therapy,
      ensuring an immune competence and a capacity to respond to vaccines.

      This is a multisite trial and is being conducted in Germany in two clinical centers:

      Cohort I:

      Charité - Universitätsmedizin Berlin Clinical Research Center for Hair and Skin Physiology
      Department of Dermatology and Allergy Schumannstr. 20/21 10117 Berlin, Germany.

      Cohort II :

      Hospital of the Johann Wolfgang Goethe-University Frankfurt am Main HIV Treatment & Research
      Unit Department of Internal Medicine II Theodor-Stern-Kai 7 60590 Frankfurt am Main -Germany
    

Intervention name(s): Transcutaneous mode of administration; Intramuscular mode of administration
Intervention type(s): Biological; Biological
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: None (Open Label)
Primary purpose: Treatment
Keywords: Transcutaneous; Vaccination; Safety; Immunogenicity; HIV; Treatment Experienced