Effective immunotherapy against canine visceral leishmaniasis with the FML-vaccine

Abstract

The potential effect of the fucose mannose ligand (FML)-vaccine on immunotherapy of canine visceral leishmaniasis was assayed on five mongrel dogs experimentally infected with Leishmania donovani and on 21 Leishmania chagasi naturally infected dogs when seropositive to FML but completely asymptomatic. The clinical signs of the experimentally infected, symptomatic dogs only disappeared after the complete vaccination. Protection was obtained in 3/5 animals that remained asymptomatic, IDR positive and parasite free, 1 year after infection. Furthermore, the asymptomatic, FML-vaccine treated dogs showed stable anti-FML IgG1 levels, increasing IgG2 levels and 79-95% of positive DTH response, during the whole experiment. Twenty-two months after complete vaccination, no obits due to visceral leishmaniasis were recorded and 90% of these dogs were still asymptomatic, healthy and parasite free. On the other hand, 37% (17/46 dogs) kala-azar obits were recorded in a control group that received no treatment during the same period, and that was FML-seropositive and asymtpomatic at the beginning of the assay. Our results indicate that the FML-vaccine was effective in the immunotherapy against visceral leishmaniasis of asymptomatic infected dogs. Normal proportions of CD4 and CD21 lymphocytes were detected in PBMC by FACS analysis, in dogs submitted to immunotherapy, suggesting their non-infectious condition. All animals showed as well significantly increased percents of CD8 lymphocytes as expected for Quillaja saponin (QuilA) vaccine treatments.

Cross-Protective Efficacy of a ProphylacticLeishmania donovaniDNA Vaccine against Visceral and Cutaneous Murine Leishmaniasis

“…This FML-saponin vaccine has been shown to induce very high levels of cross-protection in dogs infected with L. chagasi (5,6,13). On the other hand, we found in the present study that the NH36 DNA vaccine induced the highest protection against both species.…”

“…Both the purified FML complex and NH36 can induce strong immune responses and significant protection against L. donovani infection in mouse models (50,51,40). FML in saponin formulation has also been shown to protect dogs in field trials as a prophylactic (5,13) or therapeutic vaccine (6). In the present study, we thus evaluated the protective immune response induced by purified L. donovani FML, recombinant NH36 (rNH36), and NH36 DNA vaccines against both L. chagasi and L. mexicana in mice.…”

Development and Clinical Trial of a Novel DNA Vaccine as Immunotherapy during Canine Leishmaniasis

“…The outcome of infection by Leishmania depends on the balance between host ability to induce immune mechanisms against Leishmania and the parasite strategies to interfere in the process of antigen presentation and thus modulate the immune response mediated by T lymphocytes [43]. Expansion in the number of CD4 + T lymphocytes subset has been correlated to a reduction in organs parasitism in dogs undergoing immunotherapy and in vaccinated animals [44,45].…”

Current Status of Veterinary Vaccines

“…A concomitant reduction in human incidence of the disease was also reported, which is likely due to the transmission-blocking properties of the vaccine (42,125). The vaccine may also have a therapeutic effect on infected dogs (22).…”