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
Autor(a) principal: | |
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Data de Publicação: | 2022 |
Outros Autores: | , , , , , , , , , , , , , , , , , , , |
Tipo de documento: | Artigo |
Idioma: | eng |
Título da fonte: | Repositório Institucional da UFMG |
Texto Completo: | 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 |
Resumo: | CNPq - Conselho Nacional de Desenvolvimento Científico e Tecnológico |
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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 instname:Universidade Federal de Minas Gerais (UFMG) instacron:UFMG |
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Universidade Federal de Minas Gerais (UFMG) |
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UFMG |
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UFMG |
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Repositório Institucional da UFMG |
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Repositório Institucional da UFMG |
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Repositório Institucional da UFMG - Universidade Federal de Minas Gerais (UFMG) |
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