Immunotherapy against visceral leishmaniasis with the nucleoside hydrolase-DNA vaccine of Leishmania donovani
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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 μg 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 μg (91%25) and 20 μg (77%25) of the DNA vaccine, and by 20 μg DNA vaccine and garlic extract (76%25) (p = 0.023). Survival was 33%25 for saline controls, 100%25 for the 100 μg vaccine, and 83 and 67%25 for the 20 μg vaccine with and without garlic extract addition, respectively. Garlic treatment alone did not reduce parasite load (p > 0.05), but increased survival (100%25). 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-γ secretion. © 2006 Elsevier Ltd. All rights reserved.
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Allium sativum; Immunotherapy; Murine leishmaniasis; Nucleoside hydrolase; Visceral leishmaniasis DNA vaccine; gamma interferon; garlic extract; immunoglobulin A; immunoglobulin G; immunoglobulin G1; immunoglobulin G2a; immunoglobulin G2b; immunoglobulin G3; immunoglobulin M; immunomodulating agent; interleukin 10; interleukin 4; nucleosidase; DNA vaccine; gamma interferon; glycosidase; immunoglobulin G; interleukin 10; interleukin 4; plant extract; protozoal vaccine; protozoon antibody; animal cell; animal experiment; animal model; animal tissue; antibody response; article; CD4+ T lymphocyte; CD8+ T lymphocyte; cell lysate; cell protection; controlled study; dose response; drug potentiation; female; humoral immunity; hypersensitivity; immunotherapy; Leishmania donovani; mouse; nonhuman; parasite examination; phenotype; priority journal; promastigote; protein secretion; spleen cell; survival rate; visceral leishmaniasis; animal; Bagg albino mouse; biosynthesis; blood; delayed hypersensitivity; garlic; immunology; Leishmania donovani; visceral leishmaniasis; Animals; Antibodies, Protozoan; Female; Garlic; Hypersensitivity, Delayed; Immunoglobulin G; Interferon Type II; Interleukin-10; Interleukin-4; Leishmania donovani; Leishmaniasis, Visceral; Mice; Mice, Inbred BALB C; N-Glycosyl Hydrolases; Plant Extracts; Protozoan Vaccines; Vaccines, DNA
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