Antígenos de Trypanosoma cruzi para la inmunoterapia de la infección
Current chemotherapeutic against Chagas disease are clearly not-up-to date,\ninadequate because of their toxic effects, generation of resistance and frequent\ninefficacy, route and long- term schedules of administration not adapted to the field\nconditions. Therefore, it is a priority to develop new...
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| Formato: | Tesis doctoral acceptedVersion |
| Lenguaje: | Español |
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Facultad de Farmacia y Bioquímica
2016
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| Acceso en línea: | http://repositoriouba.sisbi.uba.ar/gsdl/cgi-bin/library.cgi?a=d&c=posgraafa&cl=CL1&d=HWA_1179 http://repositoriouba.sisbi.uba.ar/gsdl/collect/posgraafa/index/assoc/HWA_1179.dir/1179.PDF |
| Aporte de: |
| Sumario: | Current chemotherapeutic against Chagas disease are clearly not-up-to date,\ninadequate because of their toxic effects, generation of resistance and frequent\ninefficacy, route and long- term schedules of administration not adapted to the field\nconditions. Therefore, it is a priority to develop new therapeutic strategies to control\nT. cruzi infection. In this Ph.D Thesis, we evaluate immunotherapy with cruzipain (Cz)\nDNA to control infection in mice infected with T. cruzi. Treatment with naked plasmid\n(d) intramuscularly, and orally Salmonella (S) as an antigens-delivery system, both in\nacute and chronic phase of the infection were carried.\nCoadministration of Cz+GM-CSF, reduced the parasitemia, increasing survival\nwith amplifying humoral and cellular response, essential for the protection of muscle\ntissue damage. Both dCz+dGM-CSF and SCz+SGM-CSF vaccines, when\nadministered during the chronic stage of infection triggered a strong cellular response\nand an improvement in overall muscle tissues state, compared with controls who had\ncharacteristic Chagas disease damage.\nWe incorporated Chagasina (Chg), the physiological inhibitor of Cz, in the\ncombined immunotherapy (SCz+SChg+SGM-CSF), improving protective efficacy\nover Cz+SGM-CSF, showing lower levels of blood parasites and a better state of\nhistological sections muscle, with a lower serum levels that are markers of muscule\ninjury. More important, the multicomponent therapeutic vaccine SChg+SCz+SGMCSF,\nadministered during the chronic phase of infection, also prevent tissue pathology.\nOur results indicate that immunotherapy of T. cruzi infection by DNA coding for\nCz, Chg and GM -CSF, administered in early and late stages of infection, stimulates\nthe immune response, reduces the load parasitic and tissue inflammation characteristic\nof the disease. SChg+SCz+SGM-CSF is a promising strategy for the treatment of\nChagas disease. |
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