DNA vaccination against the parasite enzyme gamma-glutamylcysteine synthetase confers protection against Leishmania donovani infection

K. C. Carter, F. L. Henriquez, S. A. Campbell, C. W. Roberts, A. Nok, A. B. Mullen, E. McFarlane

Research output: Contribution to journalArticle

22 Citations (Scopus)

Abstract

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 (pVAX-gamma GCS) 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 pVAX-gamma GCS 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. (C) 2007 Elsevier Ltd. All rights reserved.

Original languageEnglish
Pages (from-to)4502-4509
Number of pages8
JournalVaccine
Volume25
Issue number22
DOIs
Publication statusPublished - 30 May 2007

Keywords

  • leishmania donovani
  • gamma-glutamylcysteine synthetase
  • vaccination
  • experimental visceral leishmaniasis
  • sodium stibogluguconate
  • BALB/C MICE
  • murine leishmaniasis
  • toxoplasma-gondii
  • major infection
  • in-vivo
  • responses
  • susceptibility
  • resistance

Cite this