Vaccination Against Cutaneous Leishmaniasis

Abstract

The different cutaneous leishmaniases are distinct in their etiology, epidemiology, transmission, and geographical distribution. In most instances cutaneous leishmaniasis is limited to one or a few skin ulcers that develop at the site where the parasites were deposited during the bite of the sandfly vector. Lesions typically heal spontaneously after several months but some lesions can be large and follow a chronic, more severe course. Protective immunity is usually acquired following cutaneous infection with Leishmania spp., so prevention of disease through prophylactic immunization appears to be feasible. Since vaccination with live, virulent parasites is associated with an unacceptable rate of adverse events, attention has turned to the use of killed or attenuated parasite vaccines and defined subunit vaccines. Whole parasite vaccines have the advantage of delivering multiple antigenic epitopes that may be necessary for initiation of a broad-based immune response. Persistent or repeated immune-stimulation by parasite antigens and/or sustained expression of interleukin-12 appear to be critical elements in the development of durable immunity. A number of purified or recombinant antigens, when co-administered with a vaccine adjuvant, appear promising as vaccine candidates against cutaneous leishmaniasis. The sustained expression of recombinant Leishmania antigens by vaccination with DNA is an attractive approach because it mimics the persistent antigenic stimulation of subclinical infection. Effective vaccine-induced immunity must generate an antigen-specific memory T cell population that, upon exposure to the infecting parasite, rapidly produces a type 1 effector T cell response that leads to interferon-gamma-mediated activation of infected macrophages to kill the intracellular parasites. This parasite-directed recall response must be prompt and of sufficient magnitude to overcome the subversive effect that the intracellular infection has on macrophage effector function. It is unlikely that vaccination against cutaneous leishmaniasis would induce sterile immunity, but a small number of parasites are likely to persist subclinically.

gp63 in Stable Cationic Liposomes Confers Sustained Vaccine Immunity to Susceptible BALB/c Mice Infected withLeishmania donovani

“…However, the limited experimental and clinical evidence available indicates that the same vaccine/antigen might not work for all cases of leishmaniasis (29,37). For example, differences have been observed with the 63-kDa (gp63) glycoprotein and with the Leishmania homologue of the receptor for activated C kinase (LACK), antigens that have received maximum attention in studies of CL treatment (36). Although vaccination with gp63, in its protein and DNA forms, has been largely unsuccessful or only partially protective, immunization with LACK induced strong protective and durable immunity against L. major (36).…”

Coencapsulation of CpG Oligodeoxynucleotides with RecombinantLeishmania majorStress-Inducible Protein 1 in Liposome Enhances Immune Response and Protection against Leishmaniasis in Immunized BALB/c Mice

“…In recent years, the results of phase 3 clinical trials of firstgeneration Leishmania vaccines showed limited efficacy in some trials (17,27,29), possibly due to the lack of a suitable adjuvant. Recombinant Leishmania major stress-inducible protein 1 (rLmSTI1), alone or combined with thiol-specific antioxidant or Leishmania elongation initiation factor and delivered as a DNA-based vaccine or mixed with different adjuvants, showed protection against leishmaniasis in murine and nonhuman primate models (4,9,28,37).…”

Reduced Pathology following Infection with TransgenicLeishmania majorExpressing Murine CD40 Ligand

“…Leishmanization remains the only effective vaccine against leishmaniasis. Vaccination of humans with virulent organisms has been largely discontinued due to safety concerns (28). We hypothesized that transgenic organisms expressing CD40L would be attenuated and induce less pathology while still providing protection against wild-type challenge.…”