DNA vaccination against the parasite enzyme gamma-glutamylcysteine synthetase confers protection against Leishmania donovani infection.
In this study the potential of using Leishmania donovani gamma-glutamylcysteine synthetase (glutamate-cysteine ligase, gamma-GCS) as a rational target for vaccine development was determined. Mice, immunised with plasmid containing the full gene sequence for gamma-GCS (pVAXgammaGCS) or plasmid alone (pVAX control), were challenged with a high dose of L. donovani amastigotes to give a stringent test of the ability of the vaccine to protect against infection. Vaccination with pVAXgammaGCS resulted in the production of specific IgG1 and IgG2a antibodies and resulted in significantly lower liver parasite burdens compared to controls. Protection was also associated with a significant increase in cell-mediated immunity, demonstrated as an increase in nitrite production by ConA stimulated splenocytes, an increase in the percentage of splenic CD3+CD4+ cells, and enhanced granuloma maturation, compared to control values.
Carter
K C
KC
Strathclyde Institute for Pharmacy and Biomedical Sciences, University of Strathclyde, Glasgow, UK. k.carter@strath.ac.uk
Henriquez
F L
FL
Campbell
S A
SA
Roberts
C W
CW
Nok
A
A
Mullen
A B
AB
McFarlane
E
E
D000818:Animals; D000913:Antibodies, Protozoan / Q000097:blood; D006224:Cricetinae; D005260:Female; D005721:Glutamate-Cysteine Ligase / Q000008:administration & dosage / Q000235:genetics / Q000276:immunology*; D007893:Leishmania donovani / Q000201:enzymology / Q000235:genetics / Q000276:immunology* / Q000472:pathogenicity; D007898:Leishmaniasis, Visceral / Q000276:immunology / Q000469:parasitology / Q000517:prevention & control*; D008213:Lymphocyte Activation; D008647:Mesocricetus; D051379:Mice; D008807:Mice, Inbred BALB C; D008969:Molecular Sequence Data; D016052:Protozoan Vaccines / Q000008:administration & dosage / Q000276:immunology; D017422:Sequence Analysis, DNA; D014611:Vaccination; D019444:Vaccines, DNA / Q000008:administration & dosage / Q000276:immunology
D000913:Antibodies, Protozoan; D016052:Protozoan Vaccines; D019444:Vaccines, DNA; D005721:Glutamate-Cysteine Ligase