The University of Southampton
University of Southampton Institutional Repository

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
55dcb4c8-3aec-42b9-945b-65b3403bb9a5
Ribeiro, Patricia
b2648e65-8bcb-4897-baa1-54076392059c
Dias, Daniel
16a50f15-945f-4d1f-b9a9-470c072c46bd
Mendonca, Debora V.C.
8a2037ac-d816-49a4-9a10-add64485a340
Fonseca Ramos, Fernanda
a285abcc-c281-4415-85da-6c99b2dffc02
Carvalho, Livia M.
9ae6268f-05b6-4def-8c5c-c91acada8fa8
de Oliveira, Daysiane
ae379cce-737b-4f4b-b04a-41f2bfd94fcd
Steiner, Bethina T.
fba186dc-c8d6-4083-80e8-d8cb1c161df0
Martins, Vivian T.
e98e64d9-a3a0-4bfb-8ad3-a39144a7c607
Perin, Luisa
fab3d591-db8b-4567-abd7-92c2df1860c6
Sanchez Machado, Amanda
c8ade693-7d20-4447-be3f-cde9b9784bc1
Santos, Thais T.O.
3ce71063-c658-41d7-96a5-d0f1237b4e90
Tavares, Grasiele S.V.
fc7d96b8-844a-4ed9-8828-a3b97c891e05
Oliviera-da-Silva, Jaoa A.
85b297d7-6ce1-4971-bda8-146621eacda4
Oliveira, Jamil S.
63223c0b-bbe8-42ec-96c9-a4a96f48fe86
Roatt, Bruno M.
83d5162d-a48a-4f4e-89e4-b6167ae34b7d
Machado-de-Avila, Ricardo A.
43c1cd0e-aac7-4c6a-a060-cda7a9ea21e8
Teixeira, Antonio L.
307e9daa-e053-46a0-ac22-679537448f2f
Humbert, Maria
82134d25-24b8-4fdd-bd1c-461683b5322e
Ferraz Coelho, E. A.
5e5a4bbe-2ad1-499d-aae2-bf3697f72924
Christodoulides, Myron
eba99148-620c-452a-a334-c1a52ba94078
Pagliara Lage, Daniela
55dcb4c8-3aec-42b9-945b-65b3403bb9a5
Ribeiro, Patricia
b2648e65-8bcb-4897-baa1-54076392059c
Dias, Daniel
16a50f15-945f-4d1f-b9a9-470c072c46bd
Mendonca, Debora V.C.
8a2037ac-d816-49a4-9a10-add64485a340
Fonseca Ramos, Fernanda
a285abcc-c281-4415-85da-6c99b2dffc02
Carvalho, Livia M.
9ae6268f-05b6-4def-8c5c-c91acada8fa8
de Oliveira, Daysiane
ae379cce-737b-4f4b-b04a-41f2bfd94fcd
Steiner, Bethina T.
fba186dc-c8d6-4083-80e8-d8cb1c161df0
Martins, Vivian T.
e98e64d9-a3a0-4bfb-8ad3-a39144a7c607
Perin, Luisa
fab3d591-db8b-4567-abd7-92c2df1860c6
Sanchez Machado, Amanda
c8ade693-7d20-4447-be3f-cde9b9784bc1
Santos, Thais T.O.
3ce71063-c658-41d7-96a5-d0f1237b4e90
Tavares, Grasiele S.V.
fc7d96b8-844a-4ed9-8828-a3b97c891e05
Oliviera-da-Silva, Jaoa A.
85b297d7-6ce1-4971-bda8-146621eacda4
Oliveira, Jamil S.
63223c0b-bbe8-42ec-96c9-a4a96f48fe86
Roatt, Bruno M.
83d5162d-a48a-4f4e-89e4-b6167ae34b7d
Machado-de-Avila, Ricardo A.
43c1cd0e-aac7-4c6a-a060-cda7a9ea21e8
Teixeira, Antonio L.
307e9daa-e053-46a0-ac22-679537448f2f
Humbert, Maria
82134d25-24b8-4fdd-bd1c-461683b5322e
Ferraz Coelho, E. A.
5e5a4bbe-2ad1-499d-aae2-bf3697f72924
Christodoulides, Myron
eba99148-620c-452a-a334-c1a52ba94078

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.

Full text not available from this repository.

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: 07 Oct 2021 01:46

Export record

Altmetrics

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

University divisions

Download statistics

Downloads from ePrints over the past year. Other digital versions may also be available to download e.g. from the publisher's website.

View more statistics

Atom RSS 1.0 RSS 2.0

Contact ePrints Soton: eprints@soton.ac.uk

ePrints Soton supports OAI 2.0 with a base URL of http://eprints.soton.ac.uk/cgi/oai2

This repository has been built using EPrints software, developed at the University of Southampton, but available to everyone to use.

We use cookies to ensure that we give you the best experience on our website. If you continue without changing your settings, we will assume that you are happy to receive cookies on the University of Southampton website.

×