Immunotherapy against visceral leishmaniasis with the nucleoside hydrolase-DNA vaccine of Leishmania donovani.
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 microg 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 microg (91%) and 20 microg (77%) of the DNA vaccine, and by 20 microg DNA vaccine and garlic extract (76%) (p=0.023). Survival was 33% for saline controls, 100% for the 100 microg vaccine, and 83 and 67% for the 20 microg 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.
Gamboa-León
R
R
Instituto de Microbiologia, Prof. Paulo de Góes, Universidade Federal do Rio de Janeiro, UFRJ, CCS, Cidade Universitária, Ilha do Fundão, Caixa Postal 68040, CEP 21941-590, Rio de Janeiro, RJ, Brazil.
Paraguai de Souza
E
E
Borja-Cabrera
G P
GP
Santos
F N
FN
Myashiro
L M
LM
Pinheiro
R O
RO
Dumonteil
E
E
Palatnik-de-Sousa
C B
CB
D000818:Animals; D000913:Antibodies, Protozoan / Q000097:blood; D005260:Female; D005737:Garlic; D006968:Hypersensitivity, Delayed / Q000209:etiology; D007074:Immunoglobulin G / Q000097:blood; D007371:Interferon-gamma / Q000096:biosynthesis; D016753:Interleukin-10 / Q000096:biosynthesis; D015847:Interleukin-4 / Q000096:biosynthesis; D007893:Leishmania donovani / Q000276:immunology*; D007898:Leishmaniasis, Visceral / Q000517:prevention & control*; D051379:Mice; D008807:Mice, Inbred BALB C; D009699:N-Glycosyl Hydrolases / Q000008:administration & dosage*; D010936:Plant Extracts / Q000494:pharmacology; D016052:Protozoan Vaccines / Q000008:administration & dosage* / Q000276:immunology; D019444:Vaccines, DNA / Q000008:administration & dosage* / Q000276:immunology
D000913:Antibodies, Protozoan; D007074:Immunoglobulin G; D010936:Plant Extracts; D016052:Protozoan Vaccines; D019444:Vaccines, DNA; D016753:Interleukin-10; D015847:Interleukin-4; D007371:Interferon-gamma; D009699:N-Glycosyl Hydrolases