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spelling 2023-11-06T20:47:34Z2023-11-06T20:47:34Z2022107114622https://doi.org/10.3390/vaccines100711462076-393Xhttp://hdl.handle.net/1843/60528https://orcid.org/0000-0001-7882-215Xhttps://orcid.org/0000-0002-7852-0300https://orcid.org/0000-0002-8394-4802https://orcid.org/0000-0002-1303-0490https://orcid.org/0000-0002-9663-4731https://orcid.org/0000-0002-6681-9014CNPq - Conselho Nacional de Desenvolvimento Científico e TecnológicoCAPES - Coordenação de Aperfeiçoamento de Pessoal de Nível SuperiorCurrently, there is no licensed vaccine to protect against human visceral leishmaniasis (VL), a potentially fatal disease caused by infection with Leishmania parasites. In the current study, a recombinant chimeric protein ChimT was developed based on T-cell epitopes identified from the immunogenic Leishmania amastigote proteins LiHyp1, LiHyV, LiHyC and LiHyG. ChimT was associated with the adjuvants saponin (Sap) or monophosphoryl lipid A (MPLA) and used to immunize mice, and their immunogenicity and protective efficacy were evaluated. Both ChimT/Sap and ChimT/MPLA induced the development of a specific Th1-type immune response, with significantly high levels of IFN-γ, IL-2, IL-12, TNF-α and GM-CSF cytokines produced by CD4+ and CD8+ T cell subtypes (p < 0.05), with correspondingly low production of anti-leishmanial IL-4 and IL-10 cytokines. Significantly increased (p < 0.05) levels of nitrite, a proxy for nitric oxide, and IFN-γ expression (p < 0.05) were detected in stimulated spleen cell cultures from immunized and infected mice, as was significant production of parasite-specific IgG2a isotype antibodies. Significant reductions in the parasite load in the internal organs of the immunized and infected mice (p < 0.05) were quantified with a limiting dilution technique and quantitative PCR and correlated with the immunological findings. ChimT/MPLA showed marginally superior immunogenicity than ChimT/Sap, and although this was not statistically significant (p > 0.05), ChimT/MPLA was preferred since ChimT/Sap induced transient edema in the inoculation site. ChimT also induced high IFN-γ and low IL-10 levels from human PBMCs isolated from healthy individuals and from VL-treated patients. In conclusion, the experimental T-cell multi-epitope amastigote stage Leishmania vaccine administered with adjuvants appears to be a promising vaccine candidate to protect against VL.engUniversidade Federal de Minas GeraisUFMGBrasilMED - DEPARTAMENTO DE CLÍNICA MÉDICAMEDICINA - FACULDADE DE MEDICINAVaccinesVacinaçãoCélulas T.PeptídeosImunidadeVisceral leishmaniasisVaccineT-cell epitopesPolypeptide-based proteinImmune responseAdjuvantsA Recombinant Chimeric Protein-Based Vaccine Containing T-Cell Epitopes from Amastigote Proteins and Combined with Distinct Adjuvants, Induces Immunogenicity and Protection against Leishmania infantum Infectioninfo:eu-repo/semantics/publishedVersioninfo:eu-repo/semantics/articlehttps://www.mdpi.com/2076-393X/10/7/1146Daniela Pagliara LageJoão Augusto Oliveira-da-silvaFernanda Fonseca RamosGrasiele de Sousa Vieira TavaresFernanda Ludolf RibeiroRaquel S. BandeiraIsabela A. G. PereiraMiguel Angel Chaves FumagalliBruno Mendes RoattRicardo A. Machado-de-ávilaMyron ChristodoulidesDanniele Luciana ValeEduardo Antonio Ferraz CoelhoVívian Tamietti MartinsFlávia P. LinharesCamila Simões de FreitasAmanda Sanchez MachadoJamile M. O. CardosoDaysiane de OliveiraNathalia Coral GalvaniMarcelo P. de Oliveiraapplication/pdfinfo:eu-repo/semantics/openAccessreponame:Repositório Institucional da UFMGinstname:Universidade Federal de Minas Gerais (UFMG)instacron:UFMGLICENSELicense.txtLicense.txttext/plain; charset=utf-82042https://repositorio.ufmg.br/bitstream/1843/60528/1/License.txtfa505098d172de0bc8864fc1287ffe22MD51ORIGINALA Recombinant Chimeric Protein-Based Vaccine Containing T-Cell Epitopes from Amastigote Proteins and Combined with Distinct Adjuvants, Induces Immunogenicity and Protection against Leishmania infantum Infection (1).pdfA Recombinant Chimeric Protein-Based Vaccine Containing T-Cell Epitopes from Amastigote Proteins and Combined with Distinct Adjuvants, Induces Immunogenicity and Protection against Leishmania infantum Infection (1).pdfapplication/pdf722875https://repositorio.ufmg.br/bitstream/1843/60528/2/A%20Recombinant%20Chimeric%20Protein-Based%20Vaccine%20Containing%20T-Cell%20Epitopes%20from%20Amastigote%20Proteins%20and%20Combined%20with%20Distinct%20Adjuvants%2c%20Induces%20Immunogenicity%20and%20Protection%20against%20Leishmania%20infantum%20Infection%20%281%29.pdfdb58700542ee62e1619bcc045dc0eb38MD521843/605282023-11-06 17:47:35.136oai:repositorio.ufmg.br:1843/60528Repositório de PublicaçõesPUBhttps://repositorio.ufmg.br/oaiopendoar:2023-11-06T20:47:35Repositório Institucional da UFMG - Universidade Federal de Minas Gerais (UFMG)false
dc.title.pt_BR.fl_str_mv A Recombinant Chimeric Protein-Based Vaccine Containing T-Cell Epitopes from Amastigote Proteins and Combined with Distinct Adjuvants, Induces Immunogenicity and Protection against Leishmania infantum Infection
title A Recombinant Chimeric Protein-Based Vaccine Containing T-Cell Epitopes from Amastigote Proteins and Combined with Distinct Adjuvants, Induces Immunogenicity and Protection against Leishmania infantum Infection
spellingShingle A Recombinant Chimeric Protein-Based Vaccine Containing T-Cell Epitopes from Amastigote Proteins and Combined with Distinct Adjuvants, Induces Immunogenicity and Protection against Leishmania infantum Infection
Daniela Pagliara Lage
Visceral leishmaniasis
Vaccine
T-cell epitopes
Polypeptide-based protein
Immune response
Adjuvants
Vacinação
Células T.
Peptídeos
Imunidade
title_short A Recombinant Chimeric Protein-Based Vaccine Containing T-Cell Epitopes from Amastigote Proteins and Combined with Distinct Adjuvants, Induces Immunogenicity and Protection against Leishmania infantum Infection
title_full A Recombinant Chimeric Protein-Based Vaccine Containing T-Cell Epitopes from Amastigote Proteins and Combined with Distinct Adjuvants, Induces Immunogenicity and Protection against Leishmania infantum Infection
title_fullStr A Recombinant Chimeric Protein-Based Vaccine Containing T-Cell Epitopes from Amastigote Proteins and Combined with Distinct Adjuvants, Induces Immunogenicity and Protection against Leishmania infantum Infection
title_full_unstemmed A Recombinant Chimeric Protein-Based Vaccine Containing T-Cell Epitopes from Amastigote Proteins and Combined with Distinct Adjuvants, Induces Immunogenicity and Protection against Leishmania infantum Infection
title_sort A Recombinant Chimeric Protein-Based Vaccine Containing T-Cell Epitopes from Amastigote Proteins and Combined with Distinct Adjuvants, Induces Immunogenicity and Protection against Leishmania infantum Infection
author Daniela Pagliara Lage
author_facet Daniela Pagliara Lage
João Augusto Oliveira-da-silva
Fernanda Fonseca Ramos
Grasiele de Sousa Vieira Tavares
Fernanda Ludolf Ribeiro
Raquel S. Bandeira
Isabela A. G. Pereira
Miguel Angel Chaves Fumagalli
Bruno Mendes Roatt
Ricardo A. Machado-de-ávila
Myron Christodoulides
Danniele Luciana Vale
Eduardo Antonio Ferraz Coelho
Vívian Tamietti Martins
Flávia P. Linhares
Camila Simões de Freitas
Amanda Sanchez Machado
Jamile M. O. Cardoso
Daysiane de Oliveira
Nathalia Coral Galvani
Marcelo P. de Oliveira
author_role author
author2 João Augusto Oliveira-da-silva
Fernanda Fonseca Ramos
Grasiele de Sousa Vieira Tavares
Fernanda Ludolf Ribeiro
Raquel S. Bandeira
Isabela A. G. Pereira
Miguel Angel Chaves Fumagalli
Bruno Mendes Roatt
Ricardo A. Machado-de-ávila
Myron Christodoulides
Danniele Luciana Vale
Eduardo Antonio Ferraz Coelho
Vívian Tamietti Martins
Flávia P. Linhares
Camila Simões de Freitas
Amanda Sanchez Machado
Jamile M. O. Cardoso
Daysiane de Oliveira
Nathalia Coral Galvani
Marcelo P. de Oliveira
author2_role author
author
author
author
author
author
author
author
author
author
author
author
author
author
author
author
author
author
author
author
dc.contributor.author.fl_str_mv Daniela Pagliara Lage
João Augusto Oliveira-da-silva
Fernanda Fonseca Ramos
Grasiele de Sousa Vieira Tavares
Fernanda Ludolf Ribeiro
Raquel S. Bandeira
Isabela A. G. Pereira
Miguel Angel Chaves Fumagalli
Bruno Mendes Roatt
Ricardo A. Machado-de-ávila
Myron Christodoulides
Danniele Luciana Vale
Eduardo Antonio Ferraz Coelho
Vívian Tamietti Martins
Flávia P. Linhares
Camila Simões de Freitas
Amanda Sanchez Machado
Jamile M. O. Cardoso
Daysiane de Oliveira
Nathalia Coral Galvani
Marcelo P. de Oliveira
dc.subject.por.fl_str_mv Visceral leishmaniasis
Vaccine
T-cell epitopes
Polypeptide-based protein
Immune response
Adjuvants
topic Visceral leishmaniasis
Vaccine
T-cell epitopes
Polypeptide-based protein
Immune response
Adjuvants
Vacinação
Células T.
Peptídeos
Imunidade
dc.subject.other.pt_BR.fl_str_mv Vacinação
Células T.
Peptídeos
Imunidade
description CNPq - Conselho Nacional de Desenvolvimento Científico e Tecnológico
publishDate 2022
dc.date.issued.fl_str_mv 2022
dc.date.accessioned.fl_str_mv 2023-11-06T20:47:34Z
dc.date.available.fl_str_mv 2023-11-06T20:47:34Z
dc.type.status.fl_str_mv info:eu-repo/semantics/publishedVersion
dc.type.driver.fl_str_mv info:eu-repo/semantics/article
format article
status_str publishedVersion
dc.identifier.uri.fl_str_mv http://hdl.handle.net/1843/60528
dc.identifier.doi.pt_BR.fl_str_mv https://doi.org/10.3390/vaccines10071146
dc.identifier.issn.pt_BR.fl_str_mv 2076-393X
dc.identifier.orcid.pt_BR.fl_str_mv https://orcid.org/0000-0001-7882-215X
https://orcid.org/0000-0002-7852-0300
https://orcid.org/0000-0002-8394-4802
https://orcid.org/0000-0002-1303-0490
https://orcid.org/0000-0002-9663-4731
https://orcid.org/0000-0002-6681-9014
url https://doi.org/10.3390/vaccines10071146
http://hdl.handle.net/1843/60528
https://orcid.org/0000-0001-7882-215X
https://orcid.org/0000-0002-7852-0300
https://orcid.org/0000-0002-8394-4802
https://orcid.org/0000-0002-1303-0490
https://orcid.org/0000-0002-9663-4731
https://orcid.org/0000-0002-6681-9014
identifier_str_mv 2076-393X
dc.language.iso.fl_str_mv eng
language eng
dc.relation.ispartof.pt_BR.fl_str_mv Vaccines
dc.rights.driver.fl_str_mv info:eu-repo/semantics/openAccess
eu_rights_str_mv openAccess
dc.format.none.fl_str_mv application/pdf
dc.publisher.none.fl_str_mv Universidade Federal de Minas Gerais
dc.publisher.initials.fl_str_mv UFMG
dc.publisher.country.fl_str_mv Brasil
dc.publisher.department.fl_str_mv MED - DEPARTAMENTO DE CLÍNICA MÉDICA
MEDICINA - FACULDADE DE MEDICINA
publisher.none.fl_str_mv Universidade Federal de Minas Gerais
dc.source.none.fl_str_mv reponame:Repositório Institucional da UFMG
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instname_str Universidade Federal de Minas Gerais (UFMG)
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institution UFMG
reponame_str Repositório Institucional da UFMG
collection Repositório Institucional da UFMG
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