Failure of a killed Leishmania amazonensis vaccine against American cutaneous leishmaniasis in Colombia

Abstract

We report the results of a double-blind, randomized, placebo-controlled clinical trial of a killed whole-cell Leishmania amazonensis candidate vaccine against American cutaneous leishmaniasis (CL) in Colombia. The trial subjects were 2597 healthy volunteers with negative leishmanin skin test (LST) selected from rural Colombian soldiers who were going to patrol endemic areas. They were randomized to receive either three doses of vaccine (n=1295) or placebo (n=1302) given at 20-day intervals. An active and passive case detection system was established to follow-up volunteers for 1 year after vaccination. Safety and efficacy of the vaccine were determined by comparing local and systemic adverse reactions after each dose and the incidence of parasitologically confirmed CL. In the vaccine and placebo groups 101 (7.7%) and 88 (6.8%) volunteers developed CL respectively. The vaccine was shown to be safe but offered no protection against CL caused by L. panamensis in the proposed vaccination schedule.

Two cases of visceral leishmaniasis in Colombia resistant to meglumine antimonial treatment

“…Organic pentavalent antimonials have been the first-line drugs for the treatment of leishmaniasis for the last six decades, and clinical resistance to these drugs has emerged as a primary obstacle to successful treatment and control 2,20,23,29 . A multiplicity of resistance mechanisms has been described: 1,2,20 Leishmania infection is classically associated with a depression of T helper type 1 (Th1) cells and preferential expansion of T helper type 2 (Th2) cells and accordingly, skewing of T helper cells towards a Th1 response is considered as a promising therapeutic strategy 32 . In the Th1 response, T cells activate macrophages by releasing the cytokines interferon (IFN)-γ and interleukin (IL)-2.…”

“…This appears to promote healing even in cases of diffuse cutaneous and mucosal leishmaniasis 13 . Three doses of killed L. amazonensis preparation alone provided no protection against CL in Colombian soldiers 13,32 . Current laboratory efforts are focused on novel antigens and adjuvants, live-attenuated vaccine, recombinant purified and subunit proteins, naked DNA, bacteria expressing Leishmania antigens and the targeting of dendritic cells 13 .…”

Cutaneous Leishmaniasis: Update on Vaccine Development

“…66 Phase 3 trial showed that 3-time intramuscular injection of the Leishvacin formula failed to mediate protection in human subjects. 21 However, more recent studies demonstrated that intranasal vaccination using the same antigens provided protection against L amazonensis and L braziliensis in a mouse and hamster model of infection, respectively, proving that the route of administration plays a critical role in the efficacy of a vaccine. 67,68 …”

Serine Proteases and Vaccines against Leishmaniasis: A Dual Role

“…However, the vaccination failed in a controlled phase III clinical trial in Colombia [5]. Three veterinary vaccines have been approved and are available against canine visceral leishmaniasis, one in Europe and two in Brazil [6].…”