Cationic solid–lipid nanoparticles are as efficient as electroporation in DNA vaccination against visceral leishmaniasis in mice

Abstract

The use of an appropriate delivery system has recently emerged as a promising approach for the development of effective vaccination against visceral leishmaniasis (VL). Here, we compare two vaccine delivery systems, namely electroporation and cationic solid-lipid nanoparticle (cSLN) formulation, to administer a DNA vaccine harbouring the L. donovani A2 antigen along with L. infantum cysteine proteinases [CPA and CPB without its unusual C-terminal extension (CPB(-CTE) )] and evaluate their potential against L. infantum challenge. Prime-boost administration of the pcDNA-A2-CPA-CPB(-CTE) delivered by either electroporation or cSLN formulation protects BALB/c mice against L. infantum challenge and that protective immunity is associated with high levels of IFN-γ and lower levels of IL-10 production, leading to a strong Th1 immune response. At all time points, the ratio of IFN-γ: IL-10 induced upon restimulation with rA2-rCPA-rCPB and F/T antigens was significantly higher in vaccinated animals. Moreover, Th2-efficient protection was elicited through a high humoral immune response. Nitric oxide production, parasite burden and histopathological analysis were also in concordance with other findings. Overall, these data indicate that similar to the electroporation delivery system, cSLNs as a nanoscale vehicle of Leishmania antigens could improve immune response, hence indicating the promise of these strategies against visceral leishmaniasis.

DNA vaccine against visceral leishmaniasis: a promising approach for prevention and control

“…Further, HbR‐DNA immunization stimulated the Th1‐type immunoprotective response in L. donovani challenged mice and hamster . Interestingly, recombinant A2 gene with CPA/CPB expressed in nonpathogenic L. tarentolae has also been reported as Th1‐type protective live vaccine . Additionally, gamma‐glutamylcysteine synthetase (γGCS) , amastigote gene , ribosomal P1 gene , ubiquitin gene , kinesin , interleukin‐12 DNA , ORFF DNA , cysteine proteinase‐30 have been shown to protect mice and multicomponent DNA , glycoprotein‐36 FML to protect dogs against L. donovani challenge.…”

Folate Functionalized PLGA Nanoparticles Loaded with Plasmid pVAX1-NH36: Mathematical Analysis of Release

“…In general, the process of pDNA encapsulation into polymeric NPs involves several steps and preparation parameters that should be modulated according to desired NPs characteristics. Experimental pDNA release from biodegradable matrices have been reported for different plasmids [34][35][36] and, to the best of our knowledge, only few efforts to mathematically describe the pDNA release kinetics have been reported, where the entire plasmid release process has been attributed to the diffusion mechanism [37]. Contrary to pDNA release kinetics, mathematical analysis of drug release from biodegradable matrices has been extensively reported in literature by considering one or more mechanisms of release [38,39].…”

Applications of Nanomaterials in Leishmaniasis: A Focus on Recent Advances and Challenges

“…Nanoparticles could provide a safe, efficacious, and efficient delivery system for vaccines. According to one study, solid lipid nanoparticles can serve as an efficient tool to synthesize leishmanial vaccine [129]. Delivering antigens and adjuvants using nanoparticles have different purposes:…”