title: Immunization with Leishmania vaccine-alum-BCG and montanide ISA 720 adjuvants induces low-grade type 2 cytokines and high levels of IgG2 subclass antibodies in the vervet monkey (Chlorocebus aethiops) model.
abstract: The availability of hundreds of adjuvants has prompted a need for identifying rational standards for the selection of adjuvant formulation based on sound immunological principles for human vaccines. As cytokines elaborated by activated T cells are required for the regulation of isotype switch during B-cell development, a study of Th2 cytokines and subclass distribution of the antibodies may shed new light on the processes involved in the polarization of the immune responses during vaccination studies. The aim of this study was to identify an appropriate Leishmania vaccine adjuvant based on low Th2 cytokine and high value IgG2 antibody responses. Groups of vervet monkeys were immunized with Leishmania donovani sonicate antigen (Ag) alone or in conjunction with alum-BCG (AlBCG), monophosphoryl lipid A (MPL) or montanide ISA 720 (MISA) as adjuvants. Following three time point intradermal injections on days 0, 28 and 42, IL-4, IL-10 and IgG antibody subclasses were quantified by enzyme-linked immunosorbent assay (ELISA) and data analysed by one-way analysis of variance, Tukey-Kramer test and Spearman's rank correlation analysis. Results indicated relatively higher IL-4 and IL-10 cytokine responses following MPL + Ag as compared to AlBCG + Ag or MISA + Ag immunization. There was a positive significant correlation between IL-4 and IL-10 levels (r = 1.000; P = 0.0167). Significantly higher IgG2 antibody responses were associated with either AlBCG + Ag or MISA + Ag as compared to MPL + Ag immunization (P < 0.05). The study concludes that both AlBCG and MISA may be used in Leishmania vaccine studies that favour low Th2 cytokine and strong IgG2 antibody responses.
authors.affiliation: Department of Tropical and Infectious Diseases, Institute of Primate Research, Nairobi, Kenya. mutisovic@yahoo.co.uk
authors.forename: J M
authors.initials: JM
authors.lastname: Mutiso
authors.forename: J C
authors.initials: JC
authors.lastname: Macharia
authors.forename: M M
authors.initials: MM
authors.lastname: Gicheru
mesh_terms: D000276:Adjuvants, Immunologic / Q000008:administration & dosage*; D000534:Alum Compounds / Q000008:administration & dosage*; D000818:Animals; D001500:BCG Vaccine / Q000276:immunology*; D002522:Chlorocebus aethiops; D016207:Cytokines / Q000096:biosynthesis*; D005260:Female; D007114:Immunization; D007074:Immunoglobulin G / Q000145:classification*; D016753:Interleukin-10 / Q000096:biosynthesis; D015847:Interleukin-4 / Q000096:biosynthesis; D054332:Leishmaniasis Vaccines / Q000276:immunology*; D008297:Male; D008353:Mannitol / Q000008:administration & dosage / Q000031:analogs & derivatives*; D009829:Oleic Acids / Q000008:administration & dosage*
chemical_list: D000276:Adjuvants, Immunologic; D000534:Alum Compounds; D001500:BCG Vaccine; D016207:Cytokines; D007074:Immunoglobulin G; D054332:Leishmaniasis Vaccines; D009829:Oleic Acids; D016753:Interleukin-10; D015847:Interleukin-4; C001681:mannide monooleate; C041524:aluminum sulfate; D008353:Mannitol