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Development of an innovative subunit vaccine against toxoplasmosis
T.T.L. Nguyen, Céline Ducournau, Rodolphe Carpentier, Didier Betbeder, Isabelle Dimier-Poisson
To cite this version:
T.T.L. Nguyen, Céline Ducournau, Rodolphe Carpentier, Didier Betbeder, Isabelle Dimier-Poisson.
Development of an innovative subunit vaccine against toxoplasmosis. Congrès Annuel de la Société Française d’Immunologie, Société Française d’Immunologie (SFI). FRA., Nov 2014, Lille, France.
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Development of an innovative subunit vaccine against toxoplasmosis
Toxoplasmosis is one of the most common parasitic infections in human with a character of high severity during cerebral (encephalitis), ocular (chorioretinitis) or congenital toxoplasmosis (abortions or fetal malformation). No vaccine is currently available; the development of effective vaccine approaches is a public health priority.
Vaccine delivery systems biodegradable as nanoparticle which aim reinforcement of antigen immunogenicity as well as the targeted delivery of antigens to immune competent cells have emerged as one of the most promising strategies to trigger an immune response to vaccine antigens.
In addition, mucosal delivered vaccines especially nasal immunization route have been interesting in the strategy of a new vaccine development against toxoplasmosis.
:
Vaccination protocol
Mice CBA/J, n =10/group 1. Control
2. Nanoparticle (DGNP) 30µg 3. T.gondii antigens (TE) 10µg 4. DGNP/TE 30µg/ 10µg
Acknowledgments: Institute of Biotechnology, Academy of Science and Technology, Vietnam
Conclusion Vaccination with the formulation DGNP/TE developed a specifically humoral and Th1/Th17 cellular immune response associated with a 100% survival of infected mice in acute toxoplasmosis and with significant reduction of 70% of brain cysts load in chronic toxoplasmosis.
The hopeful result engages to validate the efficiency of vaccine candidate in livestock. This study provides evidence of the potential of this delivery system for the development of new vaccines against a range of pathogens.
Aim Evaluation in vivo of the efficacy of an optimal nanoparticle/antigens formulation after nasal vaccination in acute and chronic models of Toxoplasma gondii infection.
3/ Protection
Survival after oral infection of mice with 120 cysts of 76K T.
gondii strain
Brain cysts load of mice orally infected with 30 cysts of 76K T.
gondii strain
The vaccine formulation DGNP/TE induced a high protection in term of survival (100%) and parasite burden (70% of reduction) against toxoplasmosis
Detection of specific anti-Toxoplasma IgG 45 days after the first immunization in serum by ELISA
Significantly higher level of total IgG in the serum of mice immunized with DGNP/TE (p<0.0001) 1/ Humoral immune response
Stimulation of splenocytes r1 month after final immunization with TE 10µg/ml in the absence or the presence of 20µg/ml of anti-CD4 or anti-CD8
mAb (n=2).
The specific secretion of IFN- γ and IL-17 was majority due to CD4+T cells and significant higher for vaccine formulation DGNP/TE
2/ Cellular immune response:
involvement of CD4+ T cell subset DGNP/TE
Polysaccharide Nanoparticle (DGNP) T.gondii Ag
(TE)
Schematic illustration of vaccine formulation
Nasal immunization Blood collection
D0 D15 D30 D45 D60 D105
Blood collection
Blood collection Cellular immune response Challenge per os with cysts
Survival Brain cyst load post-infection
Céline Ducournau
a, Thi Thanh Loi Nguyen
a, Rodolphe Carpentier
b, Didier Betbeder
b, Isabelle Dimier-Poisson
a*
a, UMR 1282 ISP Université-INRA Immunologie Parasitaire et Vaccinologie, Biothérapies Anti-Infectieuses, Université François Rabelais, UFR des Sciences Pharmaceutiques, 31 avenue Monge, 37200 Tours, France.
* Corresponding author, Tel: +33 2 47 36 71 83 dimier@univ-tours.fr
b,EA 4483, Laboratoire de Physiologie, faculté de Médecine pôle recherche, Université de Lille 2, 1 place Verdun, 59000 Lille, France
Confocal analysis of the delivery of TE (FITC) in epithelial cells (16HBE) by nanoparticles at 15 and 60 min
60 min 15 min
RESULTS
Th1
Stimulation of splenocytes 1 month after final immunization with TE 10µg/ml (n=6)
Th2
Th17
2/ Cellular immune response:
Th1/Th17 cytokine profil after vaccination
