title: Safety and skin delayed-type hypersensitivity response in vervet monkeys immunized with Leishmania donovani sonicate antigen delivered with adjuvants.
abstract: In this study, we report on the safety and skin delayed-type hypersensitivity (DTH), responses of the Leishmania donovani whole cell sonicate antigen delivered in conjunction with alum-BCG (AlBCG), Montanide ISA 720 (MISA) or Monophosphoryl lipid A (MPLA) in groups of vervet monkeys. Following three intradermal injections of the inoculums on days 0, 28 and 42, safety and DTH responses were assessed. Preliminary tumor necrosis factor alpha (TNF-α) and interferon gamma (IFN-γ) levels were also measured and these were compared with DTH. Only those animals immunized with alum-BCG reacted adversely to the inoculum by producing ulcerative erythematous skin indurations. Non-parametric analysis of variance followed by a post-test showed significantly higher DTH responses in the MISA+Ag group compared with other immunized groups (p < 0.001). The MPLA+Ag group indicated significantly lower DTH responses to the sonicate antigen compared with the AlBCG+Ag group. There was a significant correlation between the DTH and cytokine responses (p < 0.0001). Based on this study we conclude that Leishmania donovani sonicate antigen containing MISA 720 is safe and is associated with a strong DTH reaction following immunization.
authors.affiliation: Institute of Primate Research, Nairobi, Kenya. mutisovic@yahoo.co.uk
authors.forename: Joshua M
authors.initials: JM
authors.lastname: Mutiso
authors.forename: John C
authors.initials: JC
authors.lastname: Macharia
authors.forename: Evans
authors.initials: E
authors.lastname: Taracha
authors.forename: Kellern
authors.initials: K
authors.lastname: Wafula
authors.forename: Hitler
authors.initials: H
authors.lastname: Rikoi
authors.forename: Michael M
authors.initials: MM
authors.lastname: Gicheru
mesh_terms: D000276:Adjuvants, Immunologic / Q000008:administration & dosage* / Q000009:adverse effects; D000818:Animals; D000953:Antigens, Protozoan / Q000008:administration & dosage*; D002522:Chlorocebus aethiops; D004797:Enzyme-Linked Immunosorbent Assay; D005260:Female; D006968:Hypersensitivity, Delayed / Q000276:immunology*; D007371:Interferon-gamma / Q000097:blood; D007893:Leishmania donovani / Q000276:immunology*; D007898:Leishmaniasis, Visceral / Q000276:immunology*; D008050:Lipid A / Q000008:administration & dosage / Q000009:adverse effects / Q000031:analogs & derivatives*; D008297:Male; D014409:Tumor Necrosis Factor-alpha / Q000097:blood
chemical_list: D000276:Adjuvants, Immunologic; D000953:Antigens, Protozoan; D008050:Lipid A; D014409:Tumor Necrosis Factor-alpha; D007371:Interferon-gamma; C048436:monophosphoryl lipid A