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

21 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 (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.

Original languageEnglish
Pages (from-to)4502-9
Number of pages8
JournalVaccine
Volume25
Issue number22
DOIs
Publication statusPublished - 30 May 2007

Fingerprint

glutamate-cysteine ligase
Glutamate-Cysteine Ligase
Leishmania donovani
plasmids
Parasites
Vaccination
Plasmids
Vaccines
vaccination
parasites
amastigotes
DNA
vaccine development
granuloma
Enzymes
Nitrites
splenocytes
enzymes
Infection
Granuloma

Keywords

  • Animals
  • Antibodies, Protozoan
  • Cricetinae
  • Female
  • Glutamate-Cysteine Ligase
  • Leishmania donovani
  • Leishmaniasis, Visceral
  • Lymphocyte Activation
  • Mesocricetus
  • Mice
  • Mice, Inbred BALB C
  • Molecular Sequence Data
  • Protozoan Vaccines
  • Sequence Analysis, DNA
  • Vaccination
  • Vaccines, DNA

Cite this

Carter, K.C ; Henriquez, F.L ; Campbell, S.A ; Roberts, C.W ; Nok, A. ; Mullen, A.B ; McFarlane, E. / DNA vaccination against the parasite enzyme gamma-glutamylcysteine synthetase confers protection against Leishmania donovani infection. In: Vaccine. 2007 ; Vol. 25, No. 22. pp. 4502-9.
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DNA vaccination against the parasite enzyme gamma-glutamylcysteine synthetase confers protection against Leishmania donovani infection. / Carter, K.C; Henriquez, F.L; Campbell, S.A; Roberts, C.W; Nok, A.; Mullen, A.B; McFarlane, E.

In: Vaccine, Vol. 25, No. 22, 30.05.2007, p. 4502-9.

Research output: Contribution to journalArticle

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AB - 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.

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KW - Mesocricetus

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KW - Mice, Inbred BALB C

KW - Molecular Sequence Data

KW - Protozoan Vaccines

KW - Sequence Analysis, DNA

KW - Vaccination

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