title: Safety and immunogenicity of a defined vaccine for the prevention of cutaneous leishmaniasis.
abstract: Healthy Colombian adult volunteers with no history of leishmaniasis were evaluated for evidence of previous subclinical infection with Leishmania based on the Montenegro skin test (MST). Twelve MST-positive subjects were enrolled in an open-label, uncontrolled clinical trial (the "MST-positive trial") and received three injections of the LEISH-F1+MPL-SE vaccine (consisting of 10 microg recombinant Leishmania polyprotein LEISH-F1 antigen [TSA+LmSTI1+LeIF]+25 microg MPL-SE adjuvant). Sixty-eight MST-negative subjects were enrolled in a randomized, double-blind, controlled trial (the "MST-negative trial") and were randomly assigned to receive three injections of either the vaccine (n=34), 10 microg LEISH-F1 protein alone (n=17), or saline placebo (n=17). In both trials, the study injections were given subcutaneously on Days 0, 28, and 56, and subjects were followed for safety and immunological endpoints. The LEISH-F1+MPL-SE vaccine was safe and well tolerated in MST-positive and MST-negative subjects. In both trials, an IFN-gamma response to the LEISH-F1 antigen at Day 84 was observed in more than half of the vaccine recipients. In the MST-negative trial, the IFN-gamma response was significantly more frequent and of greater magnitude in vaccine recipients than in protein-alone or placebo recipients. An IgG antibody response to LEISH-F1 was observed in all vaccine recipients. In both trials, delayed-type hypersensitivity (DTH) to LEISH-F1 was observed in most of the vaccine recipients. In the MST-negative trial, DTH was significantly higher in vaccine than placebo recipients. These clinical trials of the first defined vaccine for leishmaniasis show that the LEISH-F1+MPL-SE vaccine is safe and immunogenic in healthy subjects with and without evidence of previous subclinical infection with Leishmania.
authors.affiliation: Programa de Estudio y Control de Enfermedades Tropicales, PECET, Universidad de Antioquia, Medellín, Colombia.
authors.forename: Iván D
authors.initials: ID
authors.lastname: Vélez
authors.forename: Katherine
authors.initials: K
authors.lastname: Gilchrist
authors.forename: Sofía
authors.initials: S
authors.lastname: Martínez
authors.forename: José R
authors.initials: JR
authors.lastname: Ramírez-Pineda
authors.forename: Jill A
authors.initials: JA
authors.lastname: Ashman
authors.forename: Fabiana P
authors.initials: FP
authors.lastname: Alves
authors.forename: Rhea N
authors.initials: RN
authors.lastname: Coler
authors.forename: Lisa Y
authors.initials: LY
authors.lastname: Bogatzki
authors.forename: Stuart J
authors.initials: SJ
authors.lastname: Kahn
authors.forename: Anna Marie
authors.initials: AM
authors.lastname: Beckmann
authors.forename: Karen D
authors.initials: KD
authors.lastname: Cowgill
authors.forename: Steven G
authors.initials: SG
authors.lastname: Reed
authors.forename: Franco M
authors.initials: FM
authors.lastname: Piazza
mesh_terms: D000293:Adolescent; D000328:Adult; D004311:Double-Blind Method; D005260:Female; D006801:Humans; D054332:Leishmaniasis Vaccines / Q000009:adverse effects / Q000276:immunology*; D016773:Leishmaniasis, Cutaneous / Q000276:immunology* / Q000517:prevention & control*; D008297:Male; D055815:Young Adult
chemical_list: D054332:Leishmaniasis Vaccines