DNA based vaccination with a cocktail of plasmids encoding immunodominant Leishmania (Leishmania) major antigens confers full protection in BALB/c mice
ABSTRACT Despite the lack of effective vaccines against parasitic diseases, the prospects of developing a vaccine against leishmaniasis are still high. With this objective, we have tested four DNA based candidate vaccines encoding to immunodominant leishmania antigens (LACKp24, TSA, LmSTI1 and CPa). These candidates have been previously reported as capable of eliciting at least partial protections in the BALB/c mice model of experimental cutaneous leishmaniasis. When tested under similar experimental conditions, all of them were able to induce similar partial protective effects, but none could induce a full protection. In order to improve the level of protection we have explored the approach of DNA based vaccination with different cocktails of plasmids encoding to the different immunodominant Leishmania antigens. A substantial increase of protection was achieved when the cocktail is composed of all of the four antigens; however, no full protection was achieved when mice were challenged with a high dose of parasite in their hind footpad. The full protection was only achieved after a challenge with a low parasitic dose in the dermis of the ear. It was difficult to determine clear protection correlates, other than the mixture of immunogens induced specific Th1 immune responses against each component. Therefore, such an association of antigens increased the number of targeted epitopes by the immune system with the prospects that the responses are at least additive if not synergistic. Even though, any extrapolation of this approach when applied to other animal or human models is rather hazardous, it undoubtedly increases the hopes of developing an effective leishmania vaccine.
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- "Reports have also demonstrated a protective role of peroxidoxin proteins against parasitic infections including Leishmania (Webb et al., 1998; Campos-Neto et al., 2002; Skeiky et al., 2002; Coler et al., 2007) and Entamoeba histolytica (Soong et al., 1995). Leishmania major thiol-specific antioxidant (TSA), homolog of Leishmania donovani peroxidoxin 2 (Pxn2), has been used as one of the components of multigenic Leishmania vaccine candidates (Skeiky et al., 2002; Coler et al., 2007; Ahmed et al., 2009). We have previously isolated three iron superoxide dismutases (Paramchuk et al., 1997; Plewes et al., 2003) and three peroxidoxins (Barr and Gedamu, 2001, 2003) from L. donovani complex in our laboratory. "
ABSTRACT: In this study, we assessed the immune response of two Leishmania donovani recombinant proteins: iron superoxide dismutase B1 (SODB1) and peroxidoxin 4 (Pxn4) in BALB/c mice. Assessment of the immunogenicity of these proteins alone or combined with Toll-like receptor 9 (TLR-9) agonist (CpG ODN) or TLR-4 agonist (GLA-SE) showed that they elicit specific antibody as well as cytokine production in response to the respective antigen in vitro. The use of adjuvants augmented immunogenicity of these antigens and more importantly, skewed the immune response to a Th1-type. These results indicate that recombinant SODB1 and Pxn4 proteins are potential vaccine candidates when administered with appropriate adjuvants.Experimental Parasitology 08/2011; 129(3):292-8. DOI:10.1016/j.exppara.2011.07.001 · 1.86 Impact Factor
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ABSTRACT: Partial response maximum likelihood (PRML) is a powerful and indispensable detection scheme for perpendicular magnetic recording channels. The performance of PRML can be improved by incorporating a noise prediction scheme into branch metric computations of the Viterbi algorithm (VA). However, the systems constructed by VA have shortcomings in the form of high complexity and cost. In this connection, a new simple detection scheme is proposed by exploiting the minimum run-length parameter d=1 and is extended to dual-detection scheme for improving the bit-error rate (BER) performance. Simulation results show that the proposed scheme has a comparable performance to noise-predictive maximum likelihood detector with less complexity when the partial response (PR) target is (1,2,1).IEEE Transactions on Magnetics 10/2003; DOI:10.1109/TMAG.2003.816478 · 1.21 Impact Factor
Conference Paper: An automatic disturbance rejection controller for matrix converter[Show abstract] [Hide abstract]
ABSTRACT: The scholars find great interest in matrix converter because of its great merits. But the researches mainly focus on open-loop control, and emphasis on the design of modulation strategy. Because the output and input lines are directly connected in matrix converter, the disturbance and unbalance of input lines affect the quality of the output waveform directly. Furthermore, in high efficient vector control systems, power converters are normally controlled to track reference output current in closed-loop. Apparently, it is necessary to control matrix converters in closed-loop. This paper establishes the model of matrix converters in d-q frame via PARK transformation. Since the closed-loop controller is relatively independent of the power electronic circuits, an automatic disturbance rejection controller (ADRC) for output current tracking is designed by applying ADRC algorithm to a matrix converter modulated by space vector modulation. Simulation results indicate that the controller have the advantages of good steady and dynamic performances, and it is strongly robust.Power Electronics Systems and Applications, 2004. Proceedings. 2004 First International Conference on; 12/2004