DNA based vaccination with a cocktail of plasmids encoding immunodominant Leishmania (Leishmania) major antigens confers full protection in BALB/c mice

Laboratory of Immunology, Vaccinology and Molecular Genetics, Institut Pasteur de Tunis, 13, Place Pasteur BP-74, 1002 Tunis-Belvedere, Tunisia.
Vaccine (Impact Factor: 3.49). 11/2008; 27(1):99-106. DOI: 10.1016/j.vaccine.2008.10.013
Source: PubMed

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. "
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