Immunochemotherapy for visceral leishmaniasis: combinatorial action of Miltefosine plus LBSapMPL vaccine improves adaptative Th1 immune response with control of splenic parasitism in experimental hamster model

Abstract

The control of human visceral leishmaniasis (VL) is hard since there are no vaccines available as well as the treatment is hampered by toxicity and resistant parasites. Furthermore, as human, and canine VL causes immunosuppression, the combination of drugs with immunostimulatory agents is interesting to upregulate the immunity, reducing side-effects, improving treatment approaches against disease. Herein, we assessed the immunochemotherapy using miltefosine along with a vaccine formulated by Leishmania braziliensis antigens + saponin + monophosphoryl lipid-A (LBSapMPL) in L. infantum-infected hamsters. Two months after infection, the animals received treatments, and after 15 days they were evaluated for the treatment effect. The potential anti-Leishmania effect of miltefosine + LBSapMPL-vaccine was revealed by a specific immune response activation reflecting in control of spleen parasitism using half the miltefosine treatment time. The treated animals also showed an increase of total and T-CD4 splenocytes producing IFN-γ and TNF-α and a decrease of interleukin-10 and anti-Leishmania circulating IgG. In addition, it was demonstrated that the control of spleen parasitism is related to the generation of a protective Th1 immune response. Hence, due to the combinatorial action of miltefosine with LBSapMPL-vaccine in immunostimulating and controlling parasitism, this immunochemotherapy protocol can be an important alternative option against canine and human VL.

Immunotherapy Using Immunogenic Mimotopes Selected by Phage Display plus Amphotericin B Inducing a Therapeutic Response in Mice Infected with Leishmania amazonensis

“…With such evolution, the hepatic parasitism tends to reduce with subsequent immunity to re-infection, whereas the splenic parasite load tends to increase and persists, when in the chronicity of infection [ 43 ]. However, despite its benefits, there are technical and scientific limitations to the applicability of this mouse model to other mammalian models, such as hamsters, dogs and humans and, in this context, they should also be evaluated before a product can be properly described as an effective vaccine and/or immunotherapeutics candidate [ 44 , 45 ]. Consequently, data presented here are preliminary and suggest that our combination involving mimotopes and AmpB showed high efficacy in a murine model.…”

Monitoring Cutaneous Leishmaniasis Lesions in Mice Undergoing Topical Miltefosine Treatment

“…In a study using L. infantum-infected hamsters, splenocytes stimulated by antigens and obtained 15 days after a 28-day oral treatment with MTF resulted in an increase in the total number of T-CD4 splenocytes that produced IFNγ and TNFα. However, there was a decrease in the total number of splenocytes that produced IL-10 [50]. As for the downregulation of VEGF, the vascular remodelling seen in lesions could explain associations between VEGF and CL.…”

Immunotherapy and immunochemotherapy in combating visceral leishmaniasis

“…Miltefosine along with immunomodulator picropliv and ketoconazole effectively treated the Leishmania donovani- infected hamsters with improved cell-mediated immune responses ( 75 ). Miltefosine in combination with L. braziliensis antigens, saponin, and monophosphoryl lipid-A enhances CD4+ T cells in splenocytes producing IFN-γ and TNF-α and a reduction of IL-10 and anti-Leishmania circulating IgG in hamsters ( 76 ). A combination of miltefosine and recombinant cysteine proteinase from Leishmania , rldccys1, significantly reduced the parasite load in infected hamsters ( 77 ).…”