4.5 Article

Immunotherapy against visceral leishmaniasis with the nucleoside hydrolase-DNA vaccine of Leishmania donovani

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VACCINE
卷 24, 期 22, 页码 4863-4873

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ELSEVIER SCI LTD
DOI: 10.1016/j.vaccine.2006.03.005

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immunotherapy; visceral leishmaniasis; murine leishmaniasis; nucleoside hydrolase; Allium sativum

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The nucleoside hydrolase (NH36) of Leishmania (L.) donovani is a vital enzyme which releases purines or pyrimidines of foreign DNA to be used in the synthesis of parasite DNA. As a bivalent DNA vaccine, the VR1012-NH36 was immunoprotective against visceral and cutaneous murine leishmaniasis. In this work we tested the immunotherapy against Leishmania (L.) chagasi infection, using two doses of 100 or 20 mu g VR1012-NH36 vaccine (i.m. route), and, as a possible immunomodulator, aqueous garlic extract (8 mg/kg/day by the i.p. route), which was effective in immunotherapy of cutaneous murine leishmaniasis. Liver parasitic load was significantly reduced following treatment with 100 mu g (91 %) and 20 mu g (77%) of the DNA vaccine, and by 20 mu g DNA vaccine and garlic extract (76%) (p = 0.023). Survival was 33% for saline controls, 100% for the 100 mu g vaccine, and 83 and 67% for the 20 mu g vaccine with and without garlic extract addition, respectively. Garlic treatment alone did not reduce parasite load (p > 0.05), but increased survival (100%). The NH36-DNA vaccine was highly effective as a new tool for the therapy and control of visceral leishmaniasis, while the mild protective effect of garlic might be related to an unspecific enhancement of IFN-gamma secretion. (c) 2006 Elsevier Ltd. All rights reserved.

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