T-cell activation of Toxoplasma gondii positive donors by maltodextrin nanoparticles formulated with killed Toxoplasma gondii

Nasal vaccination with killed tachyzoites from Toxoplasma gondii loaded in lipidated maltodextrin nanoparticles (NPL/T.gondii) has been shown to induce protection against lethal T.gondii infection in mice, sheep and squirrel monkeys. This protection was related to a unique T-cell mediated response (Th1 and Th17). In immunocompetent humans T.gondii infection is generally asymptomatic but leads to the formation of cysts in several organs. These cysts may reactivate during episodes of immunosuppression, owing to a Th1 immune exhaustion, leading to numerous complications. The objectives of the current study were to assess whether NPL/T. gondii vaccine can stimulate a specific IFN-γ secretion on peripheral blood mononuclear cells (PBMC) of Toxo-positive donors, in order to potentially prevent reactivation of the parasite. By using enzyme-linked immunospot (ELISpot) assays, the frequency of IFN-γ producing cells was quantified after 72 h of stimulation. This stimulation was specific of the Toxo + donors' memory T-cells. The uptake of this formulation by PBMCs was evaluated using flow cytometry, more particularly in T lymphocytes (CD3 + CD4 + and CD3 + CD8 +), B lymphocytes (CD3- CD19 +) and natural killer cells (CD3- CD56 +). Surprisingly, a lower antigen uptake was observed in all cell populations from Toxo + donors compared with the seronegative ones. Further in vitro analysis revealed that the early specific IFN-γ secretion by stimulated memory cells from Toxo-positive donors inhibited the endocytosis mechanism, therefore lowering their own vaccine uptake. These results suggest that NPL/T.gondii formulation can specifically trigger the existing Th1 immune response in positive donors, reinforcing their ability to control infection and reactivation.