Safety and immunogenicity of a defined vaccine for the prevention of cutaneous leishmaniasis

• Published in: Vaccine 2009-12, Vol.28 (2), p.329-337
• Main Authors: Vélez, Iván D, Gilchrist, Katherine, Martínez, Sofía, Ramírez-Pineda, José R, Ashman, Jill A, Alves, Fabiana P, Coler, Rhea N, Bogatzki, Lisa Y, Kahn, Stuart J, Beckmann, Anna Marie, Cowgill, Karen D, Reed, Steven G, Piazza, Franco M
• Format: Article
• Language: English
• Subjects: Adjuvants; Adolescent; Adult; Allergy and Immunology; Antigens; Clinical trials; Cutaneous; Double-Blind Method; Female; Humans; Hypersensitivity; Immunogenicity; Immunologic; Infections; Leishmania; Leishmaniasis; Leishmaniasis vaccines; Leishmaniasis Vaccines - adverse effects; Leishmaniasis Vaccines - immunology; Leishmaniasis, Cutaneous - immunology; Leishmaniasis, Cutaneous - prevention & control; Male; Parasites; Proteins; Tropical diseases; Vaccines; Vector-borne diseases; Young Adult
• ISSN: 0264-410X; 1873-2518
• DOI: 10.1016/j.vaccine.2009.10.045

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 μg recombinant Leishmania polyprotein LEISH-F1 antigen [TSA + LmSTI1 + LeIF] + 25 μg 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 μg 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-γ 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-γ 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.