Human-applicable dendrigraft poly- l -lysine-based nanoparticle-coated Plasmodium yoelii -transamidase DNA vaccine is immunogenic and protective as the polyethylenimine-based formulation

Abstract

The objective was to assess the immunoequivalence and protective efficacy of the novel, relatively safe dendrigraft poly-l-lysine-based nanoparticle formulation in comparison to the non-degradable polyethylenimine-based system. Groups of 6-week-old female C57BL/6 mice were immunized three times biweekly. Each mouse received 100 µg of the Plasmodium yoelii GPI8p-transamidase PyTAM formulated with nanoball that consisted of PyTAM/PEI/γ-PGA or PyTAM/DGL/γ-PGA and their respective nanoparticle-coated blank vector controls. Two weeks after the last immunization, the humoral responses and cellular immune response were assessed. The survival and parasitemia were evaluated in each group challenged intraperitoneally with 10⁶ of a lethal strain of P. yoelii 17XL-parasitized red blood cells. Mice immunized with PyTAM/PEI/γ-PGA or PyTAM/DGL/γ-PGA showed similar survival rates, humoral responses and T helper 1 pro-inflammatory cellular immune responses in vivo and ex vivo. In particular, the PyTAM/DGL/γ-PGA formulation showed a significant increase in conventional dendritic cells in the spleen, which were consistently associated with high interleukin-12 production, the driver of the T helper 1 response. We show that the substitution of non-degradable polyethylenimine with the biodegradable dendrigraft poly-l-lysine in the nanoparticle formulation is immunoequivalent and elicits protective immunity against the lethal strain of P. yoelii. Therefore, this new gene-delivery vehicle with a good safety profile presents an exciting prospect for application in vaccination strategies.