Porous nanoparticles as delivery system of complex antigens for an effective vaccine against acute and chronic Toxoplasma gondii infection.
Development of sub-unit mucosal vaccines requires the use of specific delivery systems or immune-modulators such as adjuvants to improve antigen immunogenicity. Nasal route for vaccine delivery by nanoparticles has attracted much interest but mechanisms triggering effective mucosal and systemic immune response are still poorly understood. Here we study the loading of porous nanoparticles (DGNP) with a total extract of Toxoplasma gondii antigens (TE), the delivery of TE by DGNP into airway epithelial, macrophage and dendritic cells, and the subsequent cellular activation. In vitro, DGNP are able to load complex antigens in a stable and quantitative manner. The outstanding amount of antigen association by DGNP is used to deliver TE in airway mucosa cells to induce a cellular maturation with an increased secretion of pro-inflammatory cytokines. Evaluation of nasal vaccine efficiency is performed in vivo on acute and chronic toxoplasmosis mouse models. A specific Th1/Th17 response is observed in vivo after vaccination with DGNP/TE. This is associated with high protection against toxoplasmosis regarding survival and parasite burden, correlated with an increased delivery of antigens by DGNP in airway mucosa cells. This study provides evidence of the potential of DGNP for the development of new vaccines against a range of pathogens.
Université de Tours, UMR1282 Infectiologie et Santé Publique, F-37000 Tours, France; INRA, UMR1282 Infectiologie et Santé Publique, F-37380 Nouzilly, France. Electronic address: dimier@univ-tours.fr.
Isabelle
I
Dimier-Poisson
Inserm, LIRIC - UMR 995, F-59000 Lille, France; Univ Lille, LIRIC - UMR 995, F-59000 Lille, France; CHRU de Lille, LIRIC - UMR 995, F-59000 Lille, France.
Rodolphe
R
Carpentier
Université de Tours, UMR1282 Infectiologie et Santé Publique, F-37000 Tours, France; INRA, UMR1282 Infectiologie et Santé Publique, F-37380 Nouzilly, France.
Thi Thanh Loi
TT
N'Guyen
Inserm, LIRIC - UMR 995, F-59000 Lille, France; Univ Lille, LIRIC - UMR 995, F-59000 Lille, France; CHRU de Lille, LIRIC - UMR 995, F-59000 Lille, France.
Fatima
F
Dahmani
Université de Tours, UMR1282 Infectiologie et Santé Publique, F-37000 Tours, France; INRA, UMR1282 Infectiologie et Santé Publique, F-37380 Nouzilly, France.
Céline
C
Ducournau
Inserm, LIRIC - UMR 995, F-59000 Lille, France; Univ Lille, LIRIC - UMR 995, F-59000 Lille, France; CHRU de Lille, LIRIC - UMR 995, F-59000 Lille, France.
Didier
D
Betbeder
D000208:Acute Disease; D000281:Administration, Intranasal; D000818:Animals; D000953:Antigens, Protozoan / Q000008:administration & dosage* / Q000276:immunology; D002460:Cell Line; D002908:Chronic Disease; D003713:Dendritic Cells / Q000378:metabolism; D004847:Epithelial Cells / Q000166:cytology / Q000378:metabolism; D005260:Female; D006801:Humans; D007111:Immunity, Cellular; D056724:Immunity, Humoral; D056747:Immunomodulation; D007962:Leukocytes / Q000378:metabolism; D008264:Macrophages / Q000378:metabolism; D051379:Mice; D016328:NF-kappa B / Q000378:metabolism; D053758:Nanoparticles / Q000737:chemistry* / Q000648:ultrastructure; D010316:Particle Size; D016052:Protozoan Vaccines / Q000276:immunology*; D020545:Respiratory Mucosa / Q000166:cytology; D012710:Serum Albumin, Bovine / Q000378:metabolism; D055672:Static Electricity; D051193:Toll-Like Receptors / Q000378:metabolism; D014122:Toxoplasma / Q000276:immunology*; D014123:Toxoplasmosis / Q000276:immunology* / Q000469:parasitology*
D000953:Antigens, Protozoan; D016328:NF-kappa B; D016052:Protozoan Vaccines; D051193:Toll-Like Receptors; D012710:Serum Albumin, Bovine
Immunotherapy; Nanoparticles; Nasal immunization; Toxoplasma gondii; Vaccine