title: Immunization with Leishmania major exogenous antigens protects susceptible BALB/c mice against challenge infection with L. major.
abstract: The potential of Leishmania major culture-derived soluble exogenous antigens (SEAgs) to induce a protective response in susceptible BALB/c mice challenged with L. major promastigotes was investigated. Groups of BALB/c mice were immunized with L. major SEAgs alone, L. major SEAgs coadministered with either alum (aluminum hydroxide gel) or recombinant murine interleukin-12 (rmIL-12), L. major SEAgs coadministered with both alum and rmIL-12, and L. major SEAgs coadministered with Montanide ISA 720. Importantly and surprisingly, the greatest and most consistent protection against challenge with L. major was seen in mice immunized with L. major SEAgs alone, in the absence of any adjuvant. Mice immunized with L. major SEAgs had significantly smaller lesions that at times contained more than 100-fold fewer parasites. When lymphoid cells from L. major SEAg-immunized mice were stimulated with leishmanial antigen in vitro, they proliferated and secreted a mixed profile of type 1 and type 2 cytokines. Finally, analyses with Western blot analyses and antibodies against three surface-expressed and secreted molecules of L. major (lipophosphoglycan, gp46/M2/PSA-2, and gp63) revealed that two of these molecules are present in L. major SEAgs, lipophosphoglycan and the molecules that associate with it and gp46/M2/PSA-2.
authors.affiliation: Department of Microbiology Immunology and Pathology, Colorado State University, Fort Collins, Colorado 80523-1619, USA.
authors.forename: Willy K
authors.initials: WK
authors.lastname: Tonui
authors.forename: J Santiago
authors.initials: JS
authors.lastname: Mejia
authors.forename: Lisa
authors.initials: L
authors.lastname: Hochberg
authors.forename: M Lamine
authors.initials: ML
authors.lastname: Mbow
authors.forename: Jeffrey R
authors.initials: JR
authors.lastname: Ryan
authors.forename: Adeline S T
authors.initials: AS
authors.lastname: Chan
authors.forename: Samuel K
authors.initials: SK
authors.lastname: Martin
authors.forename: Richard G
authors.initials: RG
authors.lastname: Titus
mesh_terms: D000276:Adjuvants, Immunologic / Q000008:administration & dosage; D000534:Alum Compounds / Q000008:administration & dosage; D000818:Animals; D000953:Antigens, Protozoan / Q000276:immunology*; D005260:Female; D006028:Glycosphingolipids / Q000276:immunology; D018664:Interleukin-12 / Q000008:administration & dosage / Q000276:immunology; D018320:Leishmania major / Q000737:chemistry / Q000276:immunology*; D016773:Leishmaniasis, Cutaneous / Q000276:immunology* / Q000517:prevention & control*; D008562:Membrane Glycoproteins / Q000276:immunology; D051379:Mice; D008807:Mice, Inbred BALB C; D015800:Protozoan Proteins / Q000276:immunology; D016052:Protozoan Vaccines / Q000737:chemistry / Q000276:immunology*; D018417:Th1 Cells / Q000276:immunology; D018418:Th2 Cells / Q000276:immunology; D014611:Vaccination
chemical_list: D000276:Adjuvants, Immunologic; D000534:Alum Compounds; D000953:Antigens, Protozoan; D006028:Glycosphingolipids; D008562:Membrane Glycoproteins; D015800:Protozoan Proteins; D016052:Protozoan Vaccines; C008290:lipophosphonoglycan; C066248:surface glycoprotein GP46-M-2, Leishmania; D018664:Interleukin-12; C041524:aluminum sulfate