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

• Published in: Vaccine Vol. 25; no. 22; pp. 4502 - 4509
• Main Authors: Carter, K.C, Henriquez, F.L, Campbell, S.A, Roberts, C.W, Nok, A, Mullen, A.B, McFarlane, E
• Format: Journal Article
• Language: English
• Published: Oxford Elsevier Ltd 30-05-2007; Elsevier
• Subjects: Allergy and Immunology; Animals; Antibodies, Protozoan - blood; Applied microbiology; Biological and medical sciences; Cricetinae; Female; Fundamental and applied biological sciences. Psychology; Gamma-glutamylcysteine synthetase; Glutamate-Cysteine Ligase - administration & dosage; Glutamate-Cysteine Ligase - genetics; Glutamate-Cysteine Ligase - immunology; Leishmania donovani; Leishmania donovani - enzymology; Leishmania donovani - genetics; Leishmania donovani - immunology; Leishmania donovani - pathogenicity; Leishmaniasis, Visceral - immunology; Leishmaniasis, Visceral - parasitology; Leishmaniasis, Visceral - prevention & control; Lymphocyte Activation; Mesocricetus; Mice; Mice, Inbred BALB C; Microbiology; Molecular Sequence Data; Protozoan Vaccines - administration & dosage; Protozoan Vaccines - immunology; Sequence Analysis, DNA; Vaccination; Vaccines, antisera, therapeutical immunoglobulins and monoclonal antibodies (general aspects); Vaccines, DNA - administration & dosage; Vaccines, DNA - immunology; Gamma-glutamylcysteine synthetase; Leishmania donovani; Vaccination; Infection; Kinetoplastida; Protozoa; Enzyme; Ligases; Parasitosis; Genetic vaccine
• ISSN: 0264-410X; 1873-2518
• DOI: 10.1016/j.vaccine.2007.03.014

Abstract In this study the potential of using Leishmania donovani gamma-glutamylcysteine synthetase (glutamate-cysteine ligase, γ-GCS) as a rational target for vaccine development was determined. Mice, immunised with plasmid containing the full gene sequence for γ-GCS (pVAXγGCS) 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 pVAXγGCS 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.