Immunogenicity and protective efficacy of a Brucella abortus L7/L12 DNA vaccine delivered via chitosan modified PLGA nanoparticles in mice

Abstract

The present study evaluated the immunogenicity and protective efficacy of the chitosan (CS)-modified poly-lactide-co-glycolic acid (PLGA) nanoparticles (NPs) delivering Brucella abortus L7/L12 DNA in a mouse model. The NPs were prepared by solvent displacement method and characterized for size, charge, morphology, cellular uptake and cytotoxicity. The cationic CS-PLGA NPs were spherical with a mean size of [~]165 nm with a positive zeta potential (+20 mV). DNA loading efficiency of 1.2% and DNA adsorption shifted zeta potential to -45 mV. In vitro studies in RAW 264.7 cell line demonstrated efficient uptake of the DNA loaded cationic NPs and expression of L7/L12 protein. Intramuscular immunization of the L7/L12 DNA vaccine loaded CS-PLGA NPs elicited both humoral and cell-mediated immunity with upregulation of Th1 and Th2 cytokines along with induction of IgG antibodies in mice. IFN-{gamma}, IL-2, and IL-4 levels were significantly (P < 0.001) higher than control group. The protective efficacy of the DNA loaded NPs against virulent B. abortus 544 infection (105 CFU) was significantly higher than that of the naked DNA (P<0.001). These findings suggest that the CS-PLGA NPs were efficiently delivered L7/L12 DNA and exhibited adjuvant potential, conferring protection against experimental murine brucellosis.