Leishmania infantum amastin protein incorporated in distinct adjuvant systems induces protection against visceral leishmaniasis

Ribeiro, Patrícia A.F.; Vale, Danniele L.; Dias, Daniel Lucas Santos; Lage, Daniela P.; Mendonça, Débora V.C.; Ramos, Fernanda F.; Carvalho, Lívia M.; Carvalho, Ana Maria Ravena Severino; Steiner, Bethina T.; Roque, Marjorie Coimbra; Oliveira‐da‐Silva, João A.; Oliveira, Jamil S.; Tavares, Grasiele S.V.; Galvani, Nathália Coral; Martins, Vívian T.; Chávez-Fumagalli, Miguel Á.; Roatt, Bruno Mendes; Moreira, Ricardo Luiz Fontes; Menezes‐Souza, Daniel; Oliveira, M. C.; Machado-de-Ávila, Ricardo Andrez; Teixeira, Antônio Lúcio; Coelho, Eduardo Antônio Ferraz

doi:10.1016/j.cyto.2020.155031

Cited by 13 publications

(8 citation statements)

References 63 publications

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“…ChimeraT induced lymphoproliferation in PBMC cultures from VL patients after treatment and from healthy subjects, in addition to stimulating IFN-γ production. In this context, ChimeraT could be considered as a promising candidate for future translational studies in humans, due to the induction of markers of immunogenicity from cells isolated from non-exposed healthy individuals, as observed in previous studies with other candidate vaccine antigens [58][59][60][61] .…”

Section: Discussionmentioning

confidence: 95%

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

et al. 2020

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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.

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Section: Discussionmentioning

confidence: 95%

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

et al. 2020

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“…Initially, spleens were collected from BALB/c mice that had been vaccinated with ChimeraT/liposome, ChimeraT/saponin, ChimeraT/saline, saline, saponin, or empty liposome but were not infected with L. infantum . Spleen cells were cultured and stimulated with ChimeraT and SLA, in order to examine the specificity of the cytokine response to the vaccinating antigen and to the parasite protein extract, respectively [ 58 , 59 , 60 , 61 , 62 , 63 ]. Spleen cell supernatants were collected, and the production of selected Th1 and Th2-type cytokines was evaluated as markers of the cellular immune response and as an indicator of the potential efficacy of the immunogen against infection by the parasites [ 64 , 65 , 66 ].…”

Section: Resultsmentioning

confidence: 99%

Liposomal Formulation of ChimeraT, a Multiple T-Cell Epitope-Containing Recombinant Protein, Is a Candidate Vaccine for Human Visceral Leishmaniasis

et al. 2020

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Background: Leishmaniases are neglected diseases caused by infection with Leishmania parasites and there are no human vaccines in use routinely. The purpose of this study was to examine the immunogenicity of ChimeraT, a novel synthetic recombinant vaccine against visceral leishmaniasis (VL), incorporated into a human-compatible liposome formulation. Methods: BALB/c mice were immunized subcutaneously with ChimeraT/liposome vaccine, ChimeraT/saponin adjuvant, or ChimeraT/saline and immune responses examined in vitro and in vivo. Results: Immunization with the ChimeraT/liposome formulation induced a polarized Th1-type response and significant protection against L. infantum infection. ChimeraT/liposome vaccine stimulated significantly high levels of interferon (IFN)-γ, interleukin (IL)-12, and granulocyte macrophage-colony stimulating factor (GM-CSF) cytokines by both CD4 and CD8 T-cells, with correspondingly lower levels of IL-4 and IL-10 cytokines. Induced antibodies were predominantly IgG2a isotype, and homologous antigen-stimulated spleen cells produced significant nitrite as a proxy for nitric oxide (NO). Furthermore, we examined a small number of treated VL patients and found higher levels of circulating anti-ChimeraT protein IgG2 antibodies, compared to IgG1 levels. Conclusions: Overall, the liposomal formulation of ChimeraT induced a protective Th1-type immune response and thus could be considered in future studies as a vaccine candidate against human VL.

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“…These proteins serve as membrane transporters that are essential for the survival inside the vertebrate cell or as signal transducers allowing for sensing the lysosomal acidic milieu. Amastins are among the most immunogenic leishmanial surface antigens for mice [118] and solicit strong immune responses in humans, which makes these proteins promising vaccine candidates [119]. The amastin repertoire is expanded in Leishmania spp.…”

Section: Discussionmentioning

confidence: 99%

Genome Analysis of Endotrypanum and Porcisia spp., Closest Phylogenetic Relatives of Leishmania, Highlights the Role of Amastins in Shaping Pathogenicity

Albanaz

Gerasimov

Shaw

et al. 2021

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While numerous genomes of Leishmania spp. have been sequenced and analyzed, an understanding of the evolutionary history of these organisms remains limited due to the unavailability of the sequence data for their closest known relatives, Endotrypanum and Porcisia spp., infecting sloths and porcupines. We have sequenced and analyzed genomes of three members of this clade in order to fill this gap. Their comparative analyses revealed only minute differences from Leishmaniamajor genome in terms of metabolic capacities. We also documented that the number of genes under positive selection on the Endotrypanum/Porcisia branch is rather small, with the flagellum-related group of genes being over-represented. Most significantly, the analysis of gene family evolution revealed a substantially reduced repertoire of surface proteins, such as amastins and biopterin transporters BT1 in the Endotrypanum/Porcisia species when compared to amastigote-dwelling Leishmania. This reduction was especially pronounced for δ-amastins, a subfamily of cell surface proteins crucial in the propagation of Leishmania amastigotes inside vertebrate macrophages and, apparently, dispensable for Endotrypanum/Porcisia, which do not infect such cells.

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Leishmania infantum amastin protein incorporated in distinct adjuvant systems induces protection against visceral leishmaniasis

Cited by 13 publications

References 63 publications

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

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

Liposomal Formulation of ChimeraT, a Multiple T-Cell Epitope-Containing Recombinant Protein, Is a Candidate Vaccine for Human Visceral Leishmaniasis

Genome Analysis of Endotrypanum and Porcisia spp., Closest Phylogenetic Relatives of Leishmania, Highlights the Role of Amastins in Shaping Pathogenicity

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