Human-applicable dendrigraft poly-l-lysine-based nanoparticle-coated Plasmodium yoelii-transamidase DNA vaccine is immunogenic and protective as the polyethylenimine-based formulation. (July 2016)

• Record Type: Journal Article
• Authors: Cherif, Mahamoud Sama; Mbanefo, Evaristus Chibunna; Shuaibu, Mohammed Nasir; Kodama, Yukinobu; Avenido, Eleonor Fundan; Campos-Alberto, Eduardo; Mizukami, Shusaku; Camara, Facely; Helegbe, Gideon Kofi; Kikuchi, Mihoko; Yanagi, Tetsuo; Sasaki, Hitoshi; Huy, Nguyen Tien; Karbwang, Juntra; Hirayama, Kenji
• Is Part Of: Journal of bioactive and compatible polymers. Volume 31:Number 4(2016:Jul.)
• Page Start: 334
• Page End: 347
• Publication Date: 2016-07
• Subjects: Nanoparticle -- GPI8p-transamidase -- dendrigraft poly-l-lysine -- polyethylenimine -- gamma polyglutamic acid -- Plasmodium yoelii -- DNA vaccine; Biomedical materials -- Periodicals; Polymers in medicine -- Periodicals; Polymers -- Periodicals; 547.7
• DOI: 10.1177/0883911515614011
• Languages: English
• ISSNs: 0883-9115

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 Py TAM formulated with nanoball that consisted of Py TAM/PEI/γ-PGA or Py TAM/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 10 6 of a lethal strain of P. yoelii 17XL -parasitized red blood cells. Mice immunized with Py TAM/PEI/γ-PGA or Py TAM/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 Py TAM/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.