The University of Southampton
University of Southampton Institutional Repository

Liposomal formulation of ChimeraT, a multiple T-Cell epitope-containing recombinant protein, is a candidate vaccine for human visceral Leishmaniasis

Liposomal formulation of ChimeraT, a multiple T-Cell epitope-containing recombinant protein, is a candidate vaccine for human visceral Leishmaniasis
Liposomal formulation of ChimeraT, a multiple T-Cell epitope-containing recombinant protein, is a candidate vaccine for human visceral Leishmaniasis

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.

ChimeraT, Liposome, Saponin, Th1-type immunity, Vaccine, Visceral leishmaniasis
1-20
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
Steiner, Bethina T.
fba186dc-c8d6-4083-80e8-d8cb1c161df0
Tavares, Grasiele S.V.
fc7d96b8-844a-4ed9-8828-a3b97c891e05
Martins, Vivian T.
e98e64d9-a3a0-4bfb-8ad3-a39144a7c607
Sanchez Machado, Amanda
c8ade693-7d20-4447-be3f-cde9b9784bc1
Oliviera-da-Silva, Jaoa A.
85b297d7-6ce1-4971-bda8-146621eacda4
Santos, Thais T.O.
3ce71063-c658-41d7-96a5-d0f1237b4e90
Freitas, Camila S.
de050131-f325-4793-920c-db2bc3b13c5d
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
Humbert, Maria
82134d25-24b8-4fdd-bd1c-461683b5322e
Christodoulides, Myron
eba99148-620c-452a-a334-c1a52ba94078
Ferraz Coelho, Eduardo Antonio
5e5a4bbe-2ad1-499d-aae2-bf3697f72924
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
Steiner, Bethina T.
fba186dc-c8d6-4083-80e8-d8cb1c161df0
Tavares, Grasiele S.V.
fc7d96b8-844a-4ed9-8828-a3b97c891e05
Martins, Vivian T.
e98e64d9-a3a0-4bfb-8ad3-a39144a7c607
Sanchez Machado, Amanda
c8ade693-7d20-4447-be3f-cde9b9784bc1
Oliviera-da-Silva, Jaoa A.
85b297d7-6ce1-4971-bda8-146621eacda4
Santos, Thais T.O.
3ce71063-c658-41d7-96a5-d0f1237b4e90
Freitas, Camila S.
de050131-f325-4793-920c-db2bc3b13c5d
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
Humbert, Maria
82134d25-24b8-4fdd-bd1c-461683b5322e
Christodoulides, Myron
eba99148-620c-452a-a334-c1a52ba94078
Ferraz Coelho, Eduardo Antonio
5e5a4bbe-2ad1-499d-aae2-bf3697f72924

Pagliara Lage, Daniela, Ribeiro, Patricia, Dias, Daniel, Mendonca, Debora V.C., Fonseca Ramos, Fernanda, Carvalho, Livia M., Steiner, Bethina T., Tavares, Grasiele S.V., Martins, Vivian T., Sanchez Machado, Amanda, Oliviera-da-Silva, Jaoa A., Santos, Thais T.O., Freitas, Camila S., Oliveira, Jamil S., Roatt, Bruno M., Machado-de-Avila, Ricardo A., Humbert, Maria, Christodoulides, Myron and Ferraz Coelho, Eduardo Antonio (2020) Liposomal formulation of ChimeraT, a multiple T-Cell epitope-containing recombinant protein, is a candidate vaccine for human visceral Leishmaniasis. Vaccines, 8 (2), 1-20, [289]. (doi:10.3390/vaccines8020289).

Record type: Article

Abstract

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.

Full text not available from this repository.

More information

Accepted/In Press date: 6 June 2020
Published date: 9 June 2020
Keywords: ChimeraT, Liposome, Saponin, Th1-type immunity, Vaccine, Visceral leishmaniasis

Identifiers

Local EPrints ID: 444399
URI: http://eprints.soton.ac.uk/id/eprint/444399
PURE UUID: 3f24de73-297f-43b2-8a6e-aeeb5a24c7f5
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: 16 Oct 2020 16:31
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: Bethina T. Steiner
Author: Grasiele S.V. Tavares
Author: Vivian T. Martins
Author: Amanda Sanchez Machado
Author: Jaoa A. Oliviera-da-Silva
Author: Thais T.O. Santos
Author: Camila S. Freitas
Author: Jamil S. Oliveira
Author: Bruno M. Roatt
Author: Ricardo A. Machado-de-Avila
Author: Maria Humbert ORCID iD
Author: Eduardo Antonio 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.

×