Download - Skin targeting for vaccine efficacy Laboratory of « Immunity and Infection » INSERM Paris, France
![Page 1: Skin targeting for vaccine efficacy Laboratory of « Immunity and Infection » INSERM Paris, France](https://reader030.vdocument.in/reader030/viewer/2022033108/56816674550346895dda0dce/html5/thumbnails/1.jpg)
CEA CHRU
CNRS
CPU INRA
INRIA INSERM
INSTITUT PASTEUR
IRD
1CEA CHRU
CNRS
CPU INRA
INRIA INSERM
INSTITUT PASTEUR
IRD
Skin targeting for vaccine efficacy
Laboratory of « Immunity and Infection »INSERMParis, France
Behazine COMBADIERE, PhDDirector of research INSERM
![Page 2: Skin targeting for vaccine efficacy Laboratory of « Immunity and Infection » INSERM Paris, France](https://reader030.vdocument.in/reader030/viewer/2022033108/56816674550346895dda0dce/html5/thumbnails/2.jpg)
CEA CHRU
CNRS
CPU INRA
INRIA INSERM
INSTITUT PASTEUR
IRD
FONDAMENTAL QUESTIONS AND NEW HOPES FOR VACCINATION
B cells
CD4 T cells
CD8 T cells
Dendritic cells
Intensity
Quality(T cells: cytokine released,
cytotoxicity, B cells: IgG, IgA)
Persistence of Memory
Localization (mucosa, skin, liver)
1- Vaccination for whom?Defining the target population History of infection and multiplicity of vaccination Other diseases in the population
2- What type of immunity ?Defining the correlates of protection differs depending of the pathogens
3- How?Adapting the route of immunization bio-diversity of antigen-presenting cells (AP Skin, Mucosa sites
![Page 3: Skin targeting for vaccine efficacy Laboratory of « Immunity and Infection » INSERM Paris, France](https://reader030.vdocument.in/reader030/viewer/2022033108/56816674550346895dda0dce/html5/thumbnails/3.jpg)
CEA CHRU
CNRS
CPU INRA
INRIA INSERM
INSTITUT PASTEUR
IRD
SKIN TARGETING OF APC DICTATES IMMUNOLOGICAL OUTCOMES
B cells
CD4 T cells
CD8 T cells
Dendritic cells
Lymph nodesStratum corneum
Epidermis
Dermis
Hypodermis
Lymphatic and blood capillary vessels
Dermal-epidermal junction
HAIR FOLLICLE
Blood vessels
Leukocytes recruitment(neutrophils,
monocytes, pDC)
Lymphatic vessels
Differential targeting of antigen-presenting cells dictates the immunological outcomes
(intensity, quality, localization)
Langerhans cells
Dermal DCLymph node
Micro- environments
![Page 4: Skin targeting for vaccine efficacy Laboratory of « Immunity and Infection » INSERM Paris, France](https://reader030.vdocument.in/reader030/viewer/2022033108/56816674550346895dda0dce/html5/thumbnails/4.jpg)
CEA CHRU
CNRS
CPU INRA
INRIA INSERM
INSTITUT PASTEUR
IRD
HAIR FOLLICLE TARGETING OF COMPOUNDS TO LANGERHANS CELLS
Stratum corneum
Hair fibre
Follicular cast
+ cyanoacrylate glue + follicular casts+ ca. 30% of stratum corneum
Vogt et al. J Invest Dermatology 2006 and Mahe J Invest Dermatology 2008
Stratum corneum
Epidermis
Dermis
Hypodermis
Lymphatic and blood capillary vessels
![Page 5: Skin targeting for vaccine efficacy Laboratory of « Immunity and Infection » INSERM Paris, France](https://reader030.vdocument.in/reader030/viewer/2022033108/56816674550346895dda0dce/html5/thumbnails/5.jpg)
CEA CHRU
CNRS
CPU INRA
INRIA INSERM
INSTITUT PASTEUR
IRD
SUITABLE SIZE OF VACCINE COMPOUNDS INTO FOLLICULAR DUCTS
5
37°C
Skin purified human CD1a+ cells (+40nm)
1500-700 nm
200 nm
40 nm
Suitable size for Langerhans cells up-take of vaccine : biodegradable or solid nanoparticles, virus like particles, small
viruses, DNA, protein/peptide-carrier
![Page 6: Skin targeting for vaccine efficacy Laboratory of « Immunity and Infection » INSERM Paris, France](https://reader030.vdocument.in/reader030/viewer/2022033108/56816674550346895dda0dce/html5/thumbnails/6.jpg)
CEA CHRU
CNRS
CPU INRA
INRIA INSERM
INSTITUT PASTEUR
IRD
Influenza-specific CD8
PROOF OF CONCEPT: PHASE I TRIAL OF AN INFLUENZA VACCINE
Influenza-specific CD4
Vogt et al. J Immunol 2008 and Combadiere et al Plos One 2010 TC routeIM route
Hair follicle Langerhans cells favors CD8 responses and also mucosal immunity but not IgG responses
![Page 7: Skin targeting for vaccine efficacy Laboratory of « Immunity and Infection » INSERM Paris, France](https://reader030.vdocument.in/reader030/viewer/2022033108/56816674550346895dda0dce/html5/thumbnails/7.jpg)
CEA CHRU
CNRS
CPU INRA
INRIA INSERM
INSTITUT PASTEUR
IRD
FROM HUMANIZED MICE TO CLINICAL TRIALS
“tailor-cut” immunization strategies could be proposed for infectious diseases: HIV, Malaria, Tuberculosis, emerging diseases and cancerEU-FP7 large-scale coordination : CUT’HIVAC project 2010-2014
Human skin Explants
Human immune cells
Immunodeficient mice
CLINICAL TRIALSPre-clinical modelsHumanized mice
![Page 8: Skin targeting for vaccine efficacy Laboratory of « Immunity and Infection » INSERM Paris, France](https://reader030.vdocument.in/reader030/viewer/2022033108/56816674550346895dda0dce/html5/thumbnails/8.jpg)
CEA CHRU
CNRS
CPU INRA
INRIA INSERM
INSTITUT PASTEUR
IRD
PERSPECTIVES Alternative methods of vaccination against infectious diseases
to increase vaccine efficacy and allow a “tailor-cut” immune response
Understanding skin immunological role for initiation and maintenance of immunity to infectious diseases
Translation of basic research using innovative preclinical models into clinical trials
5 Phase I/II/IIa clinical trials are planned for 2011-2014:
o Preventive and therapeutic HIV vaccine (3 trials): DNA-GTU® technology (FIT-Biotech) by TC, ID, IM or combined routes
o Influenza vaccination in adults and in elderly (2 trials) : trivalent influenza vaccine by TC, ID and IM routes