Navegando por Palavras-chave "chagas disease"

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    Comparative evaluation of therapeutic DNA vaccines against Trypanosoma cruzi in mice
    (Wiley-Blackwell, 2007-08-01) Sanchez-Burgos, Gilma; Mezquita-Vega, R. Gabino; Escobedo-Ortegon, Javier; Ramirez-Sierra, Maria Jesus; Arjona-Torres, Arletty; Ouaissi, Ali; Rodrigues, Mauricio Martins [UNIFESP]; Dumonteil, Eric; Univ Autonoma Yucatan; INSERM; Universidade Federal de São Paulo (UNIFESP)
    Chagas disease, caused by the protozoan parasite Trypanosoma cruzi, is a major public health problem in most of Latin America. A key priority is the development of new treatments, due to the poor efficacy of current ones. We report here the comparative evaluation of therapeutic DNA vaccines encoding various T. cruzi antigens. ICR mice infected with 500 parasites intraperitoneally were treated at 5 and 12 days postinfection with 20 mu g of plasmid DNA encoding T. cruzi antigens TSA-1, TS, ASP-2-like, Tc52 or Tc24. Treatment with plasmid encoding TS and/or ASP-2-like antigens had no significant effect on parasitemia or survival. Treatment with Tc52 DNA significantly reduced parasitemia, as well as cardiac parasite burden, and improved survival, although myocarditis was not significantly affected. Finally, treatment with plasmids encoding Tc24 and TSA-1 induced the most complete control of disease as evidenced by significant reductions in parasitemia, mortality, myocarditis and heart parasite burden. These data demonstrate that therapeutic vaccine efficacy is dependent on the antigen and suggest that DNA vaccines encoding Tc24, TSA-1, and Tc52 represent the best candidates for further studies of a therapeutic vaccine against Chagas disease.
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    An exploration of the genetic robustness landscape of surface protein families in the human protozoan parasite trypanosoma cruzi
    (Ieee-inst Electrical Electronics Engineers Inc, 2007-09-01) Azuaje, Francisco; Ramirez, Jose Luis; Silveira, Jos Franco da; Univ Ulster; IDEA; Universidade Federal de São Paulo (UNIFESP)
    The ability of genes to be robust to mutations at the codon level has been suggested as a key factor for understanding adaptation features. It has been proposed that genes relevant to host-parasite interactions will tend to exhibit high volatility or antirobust patterns, which may be related to the capacity of the parasite to evade the host immune system. We compared two superfamilies of surface proteins, trans-sialidase (TS)-like proteins and putative surface protein dispersed gene family-1 (DGF-1), in the parasite Trypanosoma cruzi in terms of a measure of gene volatility. We proposed alternative codon robustness indicators based on cross entropy and impurity of amino acids encoded by point-mutations, which were compared to a volatility estimator previously published. This allowed us to present a more detailed description of the differences between families. A significant difference was observed in terms of these scores, with the TS-MVar1 and the DGF-1 families showing the highest and lowest gene volatility values respectively. the cross entropy and impurity estimators suggest that the MVar1 levels of volatility are linearly correlated with their capacity to generate diverse sets of amino acids as a consequence of potential mutations. This study indicates the feasibility of applying different measures of genetic robustness to detect variations between potential drug targets at the protein level.