A candidate vaccine for human visceral leishmaniasis based on a specific T cell epitope-containing chimeric protein protects mice against Leishmania infantum infection

Abstract

Leishmaniases are neglected diseases caused by infection with Leishmania parasites and there are currently no prophylactic vaccines. In this study, we designed in silico a synthetic recombinant vaccine against visceral leishmaniasis (VL) called ChimeraT, which contains specific T-cell epitopes from Leishmania Prohibitin, Eukaryotic Initiation Factor 5a and the hypothetical LiHyp1 and LiHyp2 proteins. Subcutaneous delivery of ChimeraT plus saponin stimulated a Th1 cell-mediated immune response and protected mice against L. infantum infection, significantly reducing the parasite load in distinct organs. ChimeraT/saponin vaccine stimulated significantly higher levels of IFN-γ, IL-12, and GM-CSF cytokines by both murine CD4 + and CD8 + T cells, with correspondingly low levels of IL-4 and IL-10. Induced antibodies were predominantly IgG2a isotype and homologous antigen-stimulated spleen cells produced significant nitrite as a proxy for nitric oxide. ChimeraT also induced lymphoproliferative responses in peripheral blood mononuclear cells from VL patients after treatment and healthy subjects, as well as higher IFN-γ and lower IL-10 secretion into cell supernatants. Thus, ChimeraT associated with a Th1 adjuvant could be considered as a potential vaccine candidate to protect against human disease.

A Chimera of Th1 Stimulatory Proteins of Leishmania donovani Offers Moderate Immunotherapeutic Efficacy with a Th1-Inclined Immune Response against Visceral Leishmaniasis

“…Hence, the ability of rLdT-E/BCG to elicit such Th1-inclined responses even after the establishment of infection endorses its potential immunotherapeutic effect to generate curative responses which was consistent with the development of protective immunity against the fatal VL infection [56]. Besides, the immunotherapy treatment with the rLdT-E/BCG vaccine candidate also conferred considerable enhancement in anti-Leishmania and anti-rLdT-E-specific IgG2 further supporting the remarkably enhanced cellular response and reduced parasitic burden [54,56,57]. The magnitude of the antibody response in rLdT-E/BCG vaccinated animals signifies the induction of protective/curative Th1 response also observed in the case of commercialized canine VL vaccines [57,58].…”

Feline Leishmaniasis Caused by Leishmania infantum: Parasite Sequencing, Seropositivity, and Clinical Characterization in an Endemic Area From Brazil

“…Depending on the region, Leishmania is transmitted by different phlebotomine sand fly vectors ( 3 ). There is no human vaccine ( 4 , 5 ) and the prevalence of leishmaniasis is closely linked to the human development index and environmental degradation ( 6 , 7 ). This zoonosis remains a serious public health problem and is recognized as one of the 20 major neglected tropical diseases ( 8 ).…”

Murine Susceptibility to Leishmania amazonensis Infection Is Influenced by Arginase-1 and Macrophages at the Lesion Site

“…Classified as a neglected tropical disease by the World Health Organization, leishmaniasis represents a great challenge in the pharmacological field due to the lack of experimental vaccine candidates with satisfactory progression in human trials until now (Lage et al, 2020). Additionally, the available CL treatment is highly toxic and not fully effective (Caridha et al, 2019).…”