Thèse de doctorat en Immunologie
Sous la direction de Béhazine Combadière.
Soutenue en 2010
à Paris 6 .
Pas de résumé disponible.
Study of immune mecanisms induced by different skin routes of immunization with particle-based vaccines
Despite positive effects on the quality of public health, vaccination is still confronted with major challenges: vaccines against chronic infections (HIV, tuberculosis), alternatives to live-attenuated vaccines, non invasive routes of vaccine administration. Harnessing the skin immune system can be a good strategy to cope with these problematic. Indeed, the skin is endowed with a unique immunological environment, it contains many efficient Antigen Presenting Cells (APCs) such as epidermal Langerhans Cells (LCs), dermal Dendritic Cells (dDCs), capable of inducing potent immune responses in vivo. I have been interested in the mechanisms intrinsic to cutaneous immunity and in the becoming of the immune responses after skin vaccination via the intradermal (ID) and Transcutaneous (TC) routes. Therefore, we used Poly (lactic)-Acid-based nanoparticles (biodegradable polymeric nanoparticles) coated with the HIV-1 p24 capsid protein and a viral vector derived from vaccinia virus, MVA (Modified Vaccina Ankara). We demonstrated that the skin route of immunization was responsible for shaping the nature and quality of the immune responses, by harnessing certain skin DCs subsets. In particular, we proved that LCs were really potent at inducing CTL responses and mucosal immunity. These unique properties of LCs would be of great interest for the development of new vaccine strategies against HIV. I developed a “humanized mouse model”, engrafted with human skin, to test skin vaccine biodistribution in vivo. This new model would allow accelerating vaccine candidates’ entry into clinical trials.