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

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.

2059-0105
Pagliara Lage, Daniela
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Ribeiro, Patricia
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Dias, Daniel
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Mendonca, Debora V.C.
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Fonseca Ramos, Fernanda
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Carvalho, Livia M.
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de Oliveira, Daysiane
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Steiner, Bethina T.
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Martins, Vivian T.
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Perin, Luisa
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Sanchez Machado, Amanda
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Santos, Thais T.O.
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Tavares, Grasiele S.V.
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Oliviera-da-Silva, Jaoa A.
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Oliveira, Jamil S.
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Roatt, Bruno M.
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Machado-de-Avila, Ricardo A.
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Teixeira, Antonio L.
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Humbert, Maria
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Ferraz Coelho, E. A.
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Christodoulides, Myron
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Pagliara Lage, Daniela
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Ribeiro, Patricia
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Dias, Daniel
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Mendonca, Debora V.C.
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Fonseca Ramos, Fernanda
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Carvalho, Livia M.
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de Oliveira, Daysiane
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Steiner, Bethina T.
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Martins, Vivian T.
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Perin, Luisa
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Sanchez Machado, Amanda
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Santos, Thais T.O.
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Tavares, Grasiele S.V.
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Oliviera-da-Silva, Jaoa A.
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Oliveira, Jamil S.
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Roatt, Bruno M.
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Machado-de-Avila, Ricardo A.
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Teixeira, Antonio L.
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Humbert, Maria
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Ferraz Coelho, E. A.
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Christodoulides, Myron
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Pagliara Lage, Daniela, Ribeiro, Patricia, Dias, Daniel, Mendonca, Debora V.C., Fonseca Ramos, Fernanda, Carvalho, Livia M., de Oliveira, Daysiane, Steiner, Bethina T., Martins, Vivian T., Perin, Luisa, Sanchez Machado, Amanda, Santos, Thais T.O., Tavares, Grasiele S.V., Oliviera-da-Silva, Jaoa A., Oliveira, Jamil S., Roatt, Bruno M., Machado-de-Avila, Ricardo A., Teixeira, Antonio L., Humbert, Maria, Ferraz Coelho, E. A. and Christodoulides, Myron (2020) A candidate vaccine for human visceral leishmaniasis based on a specific T cell epitope-containing chimeric protein protects mice against Leishmania infantum infection. NPJ Vaccines, 5 (1), [75]. (doi:10.1038/s41541-020-00224-0).

Record type: Article

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.

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More information

Accepted/In Press date: 21 July 2020
Published date: 13 August 2020
Additional Information: © The Author(s) 2020.

Identifiers

Local EPrints ID: 444546
URI: http://eprints.soton.ac.uk/id/eprint/444546
ISSN: 2059-0105
PURE UUID: a23eafa0-f232-4a84-9e0e-f4560cfc5484
ORCID for Maria Humbert: ORCID iD orcid.org/0000-0002-5728-6981
ORCID for Myron Christodoulides: ORCID iD orcid.org/0000-0002-9663-4731

Catalogue record

Date deposited: 23 Oct 2020 16:32
Last modified: 17 Mar 2024 03:35

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Contributors

Author: Daniela Pagliara Lage
Author: Patricia Ribeiro
Author: Daniel Dias
Author: Debora V.C. Mendonca
Author: Fernanda Fonseca Ramos
Author: Livia M. Carvalho
Author: Daysiane de Oliveira
Author: Bethina T. Steiner
Author: Vivian T. Martins
Author: Luisa Perin
Author: Amanda Sanchez Machado
Author: Thais T.O. Santos
Author: Grasiele S.V. Tavares
Author: Jaoa A. Oliviera-da-Silva
Author: Jamil S. Oliveira
Author: Bruno M. Roatt
Author: Ricardo A. Machado-de-Avila
Author: Antonio L. Teixeira
Author: Maria Humbert ORCID iD
Author: E. A. Ferraz Coelho

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