A clinical trial to evaluate the safety and immunogenicity of the LEISH-F1+MPL-SE vaccine when used in combination with sodium stibogluconate for the treatment of mucosal leishmaniasis.
Adult patients with mucosal leishmaniasis (ML) were enrolled in a randomized, double-blind, placebo-controlled, dose-escalating clinical trial and were randomly assigned to receive three injections of either the LEISH-F1+MPL-SE vaccine (consisting of 5, 10, or 20 μg recombinant Leishmania polyprotein LEISH-F1 antigen+25 μg MPL(®)-SE adjuvant) (n=36) or saline placebo (n=12). The study injections were given subcutaneously on Days 0, 28, and 56, and the patients were followed through Day 336 for safety, immunological, and clinical evolution endpoints. All patients received standard chemotherapy with sodium stibogluconate starting on Day 0. The vaccine was safe and well tolerated, and induced both humoral and cell-mediated immune responses. Furthermore, intracellular cytokine staining showed an increase in the proportion of memory LEISH-F1-specific IL-2(+) CD4 T-cells after vaccination, which was associated with clinical cure. This clinical trial shows that the LEISH-F1+MPL-SE vaccine is safe and immunogenic in patients with ML.
Llanos-Cuentas
Alejandro
A
Instituto de Medicina Tropical Alexander von Humboldt, Universidad Peruana Cayetano Heredia, Lima, Peru.
Calderón
Wessmark
W
Cruz
María
M
Ashman
Jill A
JA
Alves
Fabiana P
FP
Coler
Rhea N
RN
Bogatzki
Lisa Y
LY
Bertholet
Sylvie
S
Laughlin
Elsa M
EM
Kahn
Stuart J
SJ
Beckmann
Anna Marie
AM
Cowgill
Karen D
KD
Reed
Steven G
SG
Piazza
Franco M
FM
D000328:Adult; D000913:Antibodies, Protozoan / Q000097:blood / Q000276:immunology; D000917:Antibody Formation; D000953:Antigens, Protozoan / Q000276:immunology*; D000967:Antimony Sodium Gluconate / Q000008:administration & dosage / Q000627:therapeutic use*; D000981:Antiprotozoal Agents / Q000008:administration & dosage / Q000627:therapeutic use*; D016207:Cytokines / Q000276:immunology; D004311:Double-Blind Method; D023381:Endpoint Determination; D005260:Female; D006801:Humans; D007074:Immunoglobulin G / Q000097:blood / Q000276:immunology; D054332:Leishmaniasis Vaccines / Q000008:administration & dosage / Q000009:adverse effects / Q000276:immunology*; D007897:Leishmaniasis, Mucocutaneous / Q000276:immunology / Q000517:prevention & control*; D008297:Male; D008875:Middle Aged; D018417:Th1 Cells / Q000276:immunology; D055815:Young Adult
D000913:Antibodies, Protozoan; D000953:Antigens, Protozoan; D000981:Antiprotozoal Agents; D016207:Cytokines; D007074:Immunoglobulin G; D054332:Leishmaniasis Vaccines; D000967:Antimony Sodium Gluconate