Vaccination with recombinant Leishmania donovani gamma-glutamylcysteine synthetase fusion protein protects against L. donovani infection.
Visceral leishmaniasis presents a serious health threat in many parts of the world. There is, therefore, an urgent need for an approved vaccine for clinical use to protect against infection. In this study, the ability of recombinant Leishmania donovani gamma-glutamyl cysteine synthetase protein (LdγGCS) alone or incorporated into a non-ionic surfactant vesicle (NIV) delivery system to protect against L. donovani infection was evaluated in a BALB/c mouse model. Immunization with LdγGCS alone or LdγGCS-NIV induced specific IgG1 and IgG2a antibodies compared to controls, with LdγGCS-NIV inducing significantly higher titers of both antibody classes (P < 0.05). Both formulations induced similar increases in splenocyte IFN-γ production following ex vivo antigen stimulation with LdγGCS compared with cells from control mice (P < 0.05). Similar levels of protection against infection were induced by LdγGCS alone and LdγGCS-NIV, based on their ability to suppress liver parasite burdens compared to control values (P < 0.01), indicating that using a carrier system did not enhance the protective responses induced by the recombinant protein. The results of this study indicate that LdγGCS may be a useful component in a vaccine against L. donovani.
Henriquez
F L
FL
School of Science, University of the West of Scotland, Paisley, UK.
Campbell
S A
SA
Roberts
C W
CW
Mullen
A B
AB
Burchmore
R
R
Carter
K C
KC
D000276:Adjuvants, Immunologic; D000818:Animals; D000913:Antibodies, Protozoan / Q000097:blood; D018699:Coated Vesicles / Q000276:immunology; D006224:Cricetinae; D004797:Enzyme-Linked Immunosorbent Assay; D005260:Female; D005721:Glutamate-Cysteine Ligase / Q000235:genetics / Q000276:immunology*; D007074:Immunoglobulin G / Q000097:blood; D007371:Interferon-gamma / Q000096:biosynthesis; D007893:Leishmania donovani / Q000235:genetics / Q000276:immunology*; D007898:Leishmaniasis, Visceral / Q000276:immunology / Q000517:prevention & control*; D008647:Mesocricetus; D051379:Mice; D008807:Mice, Inbred BALB C; D016052:Protozoan Vaccines / Q000008:administration & dosage / Q000276:immunology; D011993:Recombinant Fusion Proteins / Q000235:genetics / Q000276:immunology*; D013154:Spleen / Q000166:cytology / Q000276:immunology; D018417:Th1 Cells / Q000276:immunology; D018418:Th2 Cells / Q000276:immunology
D000276:Adjuvants, Immunologic; D000913:Antibodies, Protozoan; D007074:Immunoglobulin G; D016052:Protozoan Vaccines; D011993:Recombinant Fusion Proteins; D007371:Interferon-gamma; D005721:Glutamate-Cysteine Ligase