Coencapsulation of CpG Oligodeoxynucleotides with RecombinantLeishmania majorStress-Inducible Protein 1 in Liposome Enhances Immune Response and Protection against Leishmaniasis in Immunized BALB/c Mice

Abstract

CpG oligodeoxynucleotides (CpG ODN) have been shown to have potent adjuvant activity for a wide range of antigens. The purpose of this study was to determine the potential benefit of using liposomes as a delivery vehicle to enhance the adjuvant activity of CpG ODN with Leishmania major stress-inducible protein 1 (LmSTI1) antigen in induction of the Th1 response in a murine model of leishmaniasis. BALB/c mice were immunized subcutaneously three times in 3-week intervals with liposomal recombinant LmSTI1 (Lip-rLmSTI1), rLmSTI1 coencapsulated with CpG ODN in a liposome (Lip-rLmSTI1-CpG ODN), rLmSTI1 plus CpG ODN in phosphate-buffered saline (PBS), rLmSTI1 plus non-CpG ODN in PBS, rLmSTI1 in PBS, empty liposome, or PBS. The intensity of infection induced by L. major promastigote challenge was measured by footpad swelling. A significant (P < 0.001) inhibition of infection in mice immunized with Lip-rLmSTI1-CpG ODN was shown compared to the other groups, and no parasite was detected in the spleens of this group 14 weeks after challenge. The highest immunoglobulin G2a (IgG2a) titer and the highest IgG2a/IgG1 ratio were also shown in the sera of mice immunized with Lip-rLmSTI1-CpG ODN before and 14 weeks after challenge. The results indicated the superiority of CpG ODN in its liposomal form over its soluble form to induce the Th1 response when used in association with rLmSTI1 antigen. It seems that using a liposome delivery system carrying CpG ODN as an adjuvant coencapsulated with Leishmania antigen plays an important role in vaccine development strategies against leishmaniasis.

CpG Oligodeoxynucleotide 2006 and Miltefosine, a Potential Combination for Treatment of Experimental Visceral Leishmaniasis

“…We did not observe any improvement over the untreated infected control groups. This is in agreement with a previous report of Badiee et al (2). The present work clearly supports the application of liposomal CpG-ODN-2006 in combination with miltefosine as a novel therapeutic approach for safer treatment of VL.…”

“…The use of CpG-ODN against leishmaniasis has been reported, especially its use as an immunomodulator or adjuvant with various immunogens (2,8,12,22). Its sequence is 5Ј-TCG TCG TTT TGT CGT TTT GTC GTT-3Ј (21), and it is known for having better efficacy in human models (14).…”

Cationic liposomes containing soluble Leishmania antigens (SLA) plus CpG ODNs induce protection against murine model of leishmaniasis

“…We have already assessed the role of CpG ODNs in enhancement of immune response against two recombinant antigens including rgp63 or rLmSTI1 when entrapped into the liposomes (Badiee et al 2008;Jaafari et al 2007). In the current study, SLA as a first generation vaccine, encapsulated in cationic liposomes with or without CpG ODNs, was used to immunize BALB/c mice.…”

Liposomal adjuvant development for leishmaniasis vaccines

“…The potential benefit of using liposomes composed of DSPC to enhance the adjuvanticity of cytidine phosphate guanosine oligodeoxynucleotides (CpG ODNs) with LmSTI1 antigen was studied. 52 BALB/c mice were immunized subcutaneously with liposomal rLmSTI1 co-encapsulated with CpG ODN. The results of footpad swelling, parasite burden in spleen, IgG2a/IgG1 ratio showed that mice immunized with liposomal rLmSTI1 and CpG ODN can be protected against infection.…”