title: Non-coding pDNA bearing immunostimulatory sequences co-entrapped with leishmanial antigens in cationic liposomes elicits almost complete protection against experimental visceral leishmaniasis in BALB/c mice.
abstract: The difficulty in making successful vaccines against leishmaniasis is partly due to lack of an appropriate adjuvant. Non-coding plasmid DNA (pDNA) bearing immunostimulatory sequences (ISS) is a potent activator of innate immunity, and can thus act as an adjuvant with vaccine antigen. We therefore evaluated the efficacy of pDNA and soluble leishmanial antigens (SLA) to protect against challenge with Leishmania donovani infection. We demonstrate that immunomodulatory activity of pDNA, which potentiated a Th1 immune responses, led to enhanced protection with SLA. Importantly, adding cationic liposomes as vehicle to the antigen, with pDNA either complexed or entrapped within, significantly increased the potentiating effect of pDNA. Further, comparison of the two vaccine formulations demonstrated an impressive increase in the protective efficacy up to two folds when both antigen and pDNA were within the vehicle. Thus, these studies establish the utility of non-coding pDNA bearing ISS as strong promoters of vaccine potency of liposomal antigens especially when co-entrapped with the antigen in cationic liposomes.
authors.affiliation: Infectious Diseases and Immunology Division, Indian Institute of Chemical Biology, 4 Raja S. C. Mullick Road, Jadavpur, Kolkata 700032, India.
authors.forename: Saumyabrata
authors.initials: S
authors.lastname: Mazumder
authors.forename: Rajesh
authors.initials: R
authors.lastname: Ravindran
authors.forename: Antara
authors.initials: A
authors.lastname: Banerjee
authors.forename: Nahid
authors.initials: N
authors.lastname: Ali
mesh_terms: D000276:Adjuvants, Immunologic / Q000008:administration & dosage*; D000818:Animals; D000953:Antigens, Protozoan / Q000276:immunology*; D016207:Cytokines / Q000096:biosynthesis; D004269:DNA, Bacterial / Q000276:immunology*; D005260:Female; D007893:Leishmania donovani / Q000276:immunology*; D007898:Leishmaniasis, Visceral / Q000276:immunology / Q000517:prevention & control*; D008081:Liposomes / Q000008:administration & dosage / Q000276:immunology*; D008099:Liver / Q000469:parasitology; D008214:Lymphocytes / Q000276:immunology; D051379:Mice; D008807:Mice, Inbred BALB C; D016052:Protozoan Vaccines / Q000276:immunology*; D013154:Spleen / Q000276:immunology / Q000469:parasitology; D018417:Th1 Cells / Q000276:immunology
chemical_list: D000276:Adjuvants, Immunologic; D000953:Antigens, Protozoan; D016207:Cytokines; D004269:DNA, Bacterial; D008081:Liposomes; D016052:Protozoan Vaccines