Our results indicated the superiority of liposomal form of CpG ODNs in order to stimulate a Th1 immune response

Our results indicated the superiority of liposomal form of CpG ODNs in order to stimulate a Th1 immune response. mice was decided. Moreover, the lesion size progress was assessed weekly by footpad HS-1371 swelling measurement. Results The HS-1371 results showed that mice immunized with Lip-SLA-PS CpG or Lip-SLA-PO CpG developed a significantly smaller footpad swelling, higher level of anti SLA IgG antibodies before and after HS-1371 challenge, and lower spleen parasite burden compared with the control groups. However, there was no significant difference between mice received Lip-SLA-PS CpG and those received Lip-SLA-PO CpG. Conclusion The results demonstrated that liposomal PO CpG ODN could be used instead of PS CpG ODN to overcome the possible drawbacks. interaction with toll-like receptor 9 (TLR9). Accelerating antigen-specific immune responses by 5-500-fold was shown when they are in close physical contact with immunogen (1-3). While human trials have yielded promising results (4, 5), clinical use of free CpG ODNs still faces several challenges which limit their effectiveness. One of the limiting factors in the success of oligonucleotide-based immunotherapeutics is rapid degradation of unmodified ODNs phosphorothioate (PO CpG) within the body. This problem is diminished by some modifications such as replacement of non-bridging oxygen with sulfur in phosphate linkages to prepare nuclease-resistant phosphorothioate analogs (PS CpG) (6). Despite backbone stabilization of CpG ODNs, PS-modi?ed ODNs are still susceptible to nuclease degradation, although at a lower rate (7). Moreover, phosphorothioate modi?cation is associated with inherent disadvantages including non-sequence speci?c toxicity, unfavorable pharmacokinetic (PK) and bio-distribution (BD), poor cellular uptake, and lack of speci?city for target cells (8-11). Administration of high doses of PS CpG has been demonstrated to result in a signi?cant acute toxicity in primates due to transient complement activation and other hemodynamic changes which, in extreme cases, may result in cardiovascular collapse and death (7). In addition, PS CpG causes long term severe side effects in mice such as induction of arthritis (12), transient splenomegaly (13), lymphoid follicle destruction (14), and PS CpG-speci?c IgM production (15) depending on the CG sequence and backbone modi?cation. There are also evidences that PS-modi?ed ODNs do not closely mimic the interaction of natural PO CpG with TLR9 (10, 16-18). Based on the mentioned reasons and TLR-4 more importantly the lower price of PO CpG compared with PS CpG, we chose PO CpG as the main adjuvant and protect it by entrapment into the liposomes. One strategy to protect and extend the activity of PO CpG is encapsulation of CpG ODNs into the liposomes (19, 20). Moreover, liposomes have been used as a delivery vehicle to provide a close association of CpG ODNs with antigens, and enhance the immune responses (19). Lipid based delivery systems are also developed to alter their pharmacokinetic characteristics and enhance immune cell targeting and facilitate intracellular uptake (21). Induction of cell-mediated immune (CMI) response to poorly immunogenic Ags is possible through encapsulation HS-1371 of Ags into the liposomes (22). Liposomes are lipid based delivery systems that have been used widely to deliver drugs, peptides, proteins, and DNA because of their appropriate properties such as inducing immune response and being safe and biodegradable (23, 24). The structures properties such as rigidity, surface charge, and epitope density are efficient in the induced immune response (25). In addition, liposomes make association between antigen and immune-adjuvant to enhance generated immune response (1, 26). candidate vaccines consisting of killed or parasite fractions have been developed based on this fact. However, they induced only limited prophylactic efficacy and stopped in the phase III of clinical trials mainly due to lack of an appropriate adjuvant (29-33). SLA, as a first generation vaccine, composed of most of the parasites soluble antigens provides a wider range of potentially protective epitopes and induces better protection than any of parasite antigens alone (34, 35). We have previously assessed the role of CpG ODNs in enhancement of immune response against two.