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1<br />Skin targeting for vaccine efficacy<br />Laboratory of « Immunity and Infection »<br />INSERM<br />Paris, France<br...
Fondamental questions and New hopes for vaccination<br />1- Vaccination for whom?<br />Defining the  target population <br...
Otherdiseases in the population</li></ul>2- What type of immunity ?<br />Defining the correlates of protection <br />diff...
Skin, Mucosa sites </li></ul>Intensity<br />Quality<br />(T cells: cytokine released, cytotoxicity, B cells: IgG, IgA)<br ...
SKIN TARGETING OF APC DICTATES IMMUNOLOGICAL OUTCOMES<br />Lymph nodes<br />HAIR FOLLICLE<br />Stratum <br />corneum<br />...
Stratum corneum<br />Follicular cast<br />Hair fibre<br />+ cyanoacrylate glue + follicular casts+ ca. 30% of stratum corn...
Suitable size of vaccine compounds intofollicularducts<br />1500-700 nm<br /><br /><br />200 nm<br /><br /><br />40 nm...
PROOF OF CONCEPT: PHASE I TRIAL OF AN INFLUENZA VACCINE<br />Influenza-specific CD8<br />TC route<br />Vogt et al. J Immun...
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2.5 behazine combadiere

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2.5 behazine combadiere

  1. 1. 1<br />Skin targeting for vaccine efficacy<br />Laboratory of « Immunity and Infection »<br />INSERM<br />Paris, France<br />Behazine COMBADIERE, PhD<br />Director of research INSERM<br />
  2. 2. Fondamental questions and New hopes for vaccination<br />1- Vaccination for whom?<br />Defining the target population <br /><ul><li>History of infection and multiplicity of vaccination
  3. 3. Otherdiseases in the population</li></ul>2- What type of immunity ?<br />Defining the correlates of protection <br />differsdepending of the pathogens<br />3- How?<br />Adapting the route of immunization<br /><ul><li>bio-diversity of antigen-presentingcells (AP
  4. 4. Skin, Mucosa sites </li></ul>Intensity<br />Quality<br />(T cells: cytokine released, cytotoxicity, B cells: IgG, IgA)<br />Persistence of Memory<br />Localization <br />(mucosa, skin, liver)<br />CD4 <br />T cells<br />Dendritic cells<br />B cells<br />CD8 <br />T cells<br />
  5. 5. SKIN TARGETING OF APC DICTATES IMMUNOLOGICAL OUTCOMES<br />Lymph nodes<br />HAIR FOLLICLE<br />Stratum <br />corneum<br />Langerhans cells<br />Lymph node<br />Micro- environments<br />Epidermis<br />Lymphatic vessels<br />Dermal-<br />epidermal<br /> junction<br />Dermal DC<br />Dermis<br /> Differential targeting of antigen-presenting cells <br /> dictates the immunological outcomes<br /> (intensity, quality, localization)<br />Lymphatic <br />and blood<br /> capillary <br />vessels<br />Hypodermis<br />Leukocytes recruitment(neutrophils, monocytes, pDC)<br />CD4 <br />T cells<br />Dendritic cells<br />B cells<br />CD8 <br />T cells<br />Blood vessels<br />
  6. 6. Stratum corneum<br />Follicular cast<br />Hair fibre<br />+ cyanoacrylate glue + follicular casts+ ca. 30% of stratum corneum<br />HAIR FOLLICLE TARGETING OF COMPOUNDS TO LANGERHANS CELLS<br />Stratum <br />corneum<br />Epidermis<br />Dermis<br />Lymphatic <br />and blood<br /> capillary <br />vessels<br />Hypodermis<br />Vogt et al. J Invest Dermatology 2006 and Mahe J Invest Dermatology 2008<br />
  7. 7. Suitable size of vaccine compounds intofollicularducts<br />1500-700 nm<br /><br /><br />200 nm<br /><br /><br />40 nm<br />37°C<br />Suitable size for Langerhans cells up-take of vaccine : <br />biodegradable or solid nanoparticles, virus like particles, small viruses, DNA, protein/peptide-carrier<br />Skin purified human CD1a+ cells (+40nm)<br />5<br />
  8. 8. PROOF OF CONCEPT: PHASE I TRIAL OF AN INFLUENZA VACCINE<br />Influenza-specific CD8<br />TC route<br />Vogt et al. J Immunol 2008 and Combadiere et al Plos One 2010<br />IM route<br />Hair follicle Langerhans cells favors CD8 responses <br />and also mucosal immunity but not IgG responses <br />Influenza-specific CD4<br />
  9. 9. FROM HUMANIZED MICE TO CLINICAL TRIALS<br />“tailor-cut” immunization strategies could be proposed for infectious diseases: <br />HIV, Malaria, Tuberculosis, emerging diseases and cancer<br />EU-FP7 large-scale coordination : CUT’HIVAC project 2010-2014<br />Pre-clinical models<br />Humanized mice <br />CLINICAL TRIALS<br />Human skin <br />Explants<br />Human immune cells<br />Immunodeficient mice<br />
  10. 10. PERSPECTIVES<br /><ul><li>Alternative methods of vaccination against infectious diseases to increase vaccine efficacy and allow a “tailor-cut” immune response
  11. 11. Understanding skin immunological role for initiation and maintenance of immunity to infectious diseases
  12. 12. Translation of basic research using innovative preclinical modelsinto clinical trials</li></ul>5 Phase I/II/IIa clinical trials are planned for 2011-2014: <br /><ul><li> Preventive and therapeutic HIV vaccine (3 trials): DNA-GTU® technology (FIT-Biotech) by TC, ID, IM or combined routes
  13. 13. Influenza vaccination in adults and in elderly (2 trials) : trivalent influenza vaccine by TC, ID and IM routes</li>

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