Targeted Delivery of Toxoplasma gondii Antigens to Dendritic Cells Promote Immunogenicity and Protective Efficiency against Toxoplasmosis

Zineb Lakhrif, Alexis Moreau, Bruno Hérault, Anne Di-Tommaso, Matthieu Juste, Nathalie Moiré, Isabelle Dimier-Poisson, Marie-Noëlle Mévélec, Nicolas Aubrey

Toxoplasmosis is a major public health problem and the development of a human vaccine is of high priority. Efficient vaccination againstToxoplasma gondiirequires both a mucosal and systemic Th1 immune response. Moreover, dendritic cells play a critical role in orchestrating the innate immune functions and driving specific adaptive immunity toT. gondii. In this study, we explore an original vaccination strategy that combines administrationviamucosal and systemic routes of fusion proteins able to target the majorT. gondiisurface antigen SAG1 to DCs using an antibody fragment single-chain fragment variable (scFv) directed against DEC205 endocytic receptor. Our results show that SAG1 targeting to DCs by scFvviaintranasal and subcutaneous administration improved protection against chronicT. gondiiinfection. A marked reduction in brain parasite burden is observed when compared with the intranasal or the subcutaneous route alone. DC targeting improved both local and systemic humoral and cellular immune responses and potentiated more specifically the Th1 response profile by more efficient production of IFN-γ, interleukin-2, IgG2a, and nasal IgA. This study provides evidence of the potential of DC targeting for the development of new vaccines against a range ofApicomplexaparasites.