Selection strategy of phage-displayed immunogens based on an in vitro evaluation of the Th1 response of PBMCs and their potential use as a vaccine against leishmania infantum infection
Autor(a) principal: | |
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Data de Publicação: | 2017 |
Outros Autores: | , , , , , , , , , , , , , , , , , |
Tipo de documento: | Artigo |
Idioma: | eng |
Título da fonte: | Repositório Institucional da UFMG |
Texto Completo: | https://doi.org/10.1186/s13071-017-2576-8 http://hdl.handle.net/1843/56622 https://orcid.org/0000-0002-7852-0300 https://orcid.org/0000-0001-6129-1719 https://orcid.org/0000-0003-4807-0457 https://orcid.org/0000-0002-8710-9265 https://orcid.org/0000-0002-3100-0009 https://orcid.org/0000-0002-6681-9014 https://orcid.org/0000-0002-6285-8163 https://orcid.org/0000-0002-4147-5614 https://orcid.org/0000-0001-5281-3263 https://orcid.org/0000-0002-9621-5422 https://orcid.org/0000-0002-1803-4861 |
Resumo: | Background: The development of a vaccine for the prevention of visceral leishmaniasis (VL) still represents a significant unmet medical need. A human vaccine can be found if one takes into consideration that many people living in endemic areas of disease are infected but do not develop active VL, including those subjects with subclinical or asymptomatic infection. Methods: In this study, a phage display was used to select phage-exposed peptides that were specific to immunoglobulin G (IgG) antibodies from asymptomatic and symptomatic VL patients, separating them from non-infected subjects. Phage clones presenting valid peptide sequences were selected and used as stimuli of peripheral blood mononuclear cells (PBMCs) obtained from both patients’ groups and controls. Those with higher interferon-gamma (IFN-γ)/interleukin (IL)-10 ratios were further selected for vaccination tests. Results: Among 17 evaluated clones, two were selected, B1 and D11, and used to immunize BALB/c mice in an attempt to further validate their in vivo protective efficacy against Leishmania infantum infection. Both clones induced partial protection against the parasite challenge, which was evidenced by the reduction of parasitism in the evaluated organs, a process mediated by a specific T helper (Th)1 immune response. Conclusions: To the best of our knowledge, this study is the first to use a rational strategy based on in vitro stimulation of human PBMCs with selected phage-displayed clones to obtain new immunogens against VL. |
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2023-07-18T20:08:13Z2023-07-18T20:08:13Z201710https://doi.org/10.1186/s13071-017-2576-81756-3305http://hdl.handle.net/1843/56622https://orcid.org/0000-0002-7852-0300https://orcid.org/0000-0001-6129-1719https://orcid.org/0000-0003-4807-0457https://orcid.org/0000-0002-8710-9265https://orcid.org/0000-0002-3100-0009https://orcid.org/0000-0002-6681-9014https://orcid.org/0000-0002-6285-8163https://orcid.org/0000-0002-4147-5614https://orcid.org/0000-0001-5281-3263https://orcid.org/0000-0002-9621-5422https://orcid.org/0000-0002-1803-4861https://orcid.org/0000-0002-6681-9014Background: The development of a vaccine for the prevention of visceral leishmaniasis (VL) still represents a significant unmet medical need. A human vaccine can be found if one takes into consideration that many people living in endemic areas of disease are infected but do not develop active VL, including those subjects with subclinical or asymptomatic infection. Methods: In this study, a phage display was used to select phage-exposed peptides that were specific to immunoglobulin G (IgG) antibodies from asymptomatic and symptomatic VL patients, separating them from non-infected subjects. Phage clones presenting valid peptide sequences were selected and used as stimuli of peripheral blood mononuclear cells (PBMCs) obtained from both patients’ groups and controls. Those with higher interferon-gamma (IFN-γ)/interleukin (IL)-10 ratios were further selected for vaccination tests. Results: Among 17 evaluated clones, two were selected, B1 and D11, and used to immunize BALB/c mice in an attempt to further validate their in vivo protective efficacy against Leishmania infantum infection. Both clones induced partial protection against the parasite challenge, which was evidenced by the reduction of parasitism in the evaluated organs, a process mediated by a specific T helper (Th)1 immune response. Conclusions: To the best of our knowledge, this study is the first to use a rational strategy based on in vitro stimulation of human PBMCs with selected phage-displayed clones to obtain new immunogens against VL.Antecedentes: O desenvolvimento de uma vacina para a prevenção da leishmaniose visceral (LV) ainda representa uma necessidade médica significativa não atendida. Uma vacina humana pode ser encontrada se levarmos em consideração que muitas pessoas que vivem em áreas endêmicas da doença estão infectadas, mas não desenvolvem LV ativa, incluindo aqueles indivíduos com infecção subclínica ou assintomática. Métodos: Neste estudo, uma exibição de fagos foi usada para selecionar peptídeos expostos a fagos que eram específicos para anticorpos imunoglobulina G (IgG) de pacientes com LV assintomáticos e sintomáticos, separando-os de indivíduos não infectados. Clones de fagos apresentando sequências peptídicas válidas foram selecionados e usados como estímulos de células mononucleares de sangue periférico (PBMCs) obtidas de grupos de pacientes e controles. Aqueles com maior relação interferon-gama (IFN-γ)/interleucina (IL)-10 foram posteriormente selecionados para testes de vacinação. Resultados: Dos 17 clones avaliados, dois foram selecionados, B1 e D11, e utilizados para imunizar camundongos BALB/c na tentativa de validar ainda mais sua eficácia protetora in vivo contra a infecção por Leishmania infantum. Ambos os clones induziram proteção parcial contra o desafio parasitário, evidenciado pela redução do parasitismo nos órgãos avaliados, processo mediado por uma resposta imune específica T helper (Th)1. Conclusões: Até onde sabemos, este estudo é o primeiro a usar uma estratégia racional baseada na estimulação in vitro de PBMCs humanas com clones exibidos em fagos selecionados para obter novos imunógenos contra a LV.Outra AgênciaengUniversidade Federal de Minas GeraisUFMGBrasilCOLTEC - COLEGIO TECNICOParasites & VectorsLeishmaniose visceralLeishmania infantumVacinasTécnicas de visualização da superfície celularImunidadeLeucócitos mononuclearesPhage displayPeripheral blood mononuclear cellsImmune responseVaccineVisceral leishmaniasisLeishmania infantumSelection strategy of phage-displayed immunogens based on an in vitro evaluation of the Th1 response of PBMCs and their potential use as a vaccine against leishmania infantum infectionEstratégia de seleção de imunógenos exibidos em fagos com base em uma avaliação in vitro da resposta Th1 de PBMCs e seu potencial uso como vacina contra a infecção por leishmania infantuminfo:eu-repo/semantics/publishedVersioninfo:eu-repo/semantics/articlehttps://parasitesandvectors.biomedcentral.com/articles/10.1186/s13071-017-2576-8Fernanda Fonseca RamosLourena Emanuele CostaDaniel Silva DiasThaís Teodoro de Oliveira SantosMarcella Rezende RodriguesDaniela Pagliara LageBeatriz Cristina Silveira SallesVívian Tamietti MartinsPatrícia Aparecida Fernandes RibeiroMiguel Angel Chávez FumagalliAna Carolina Silva DiasPatrícia Terra AlvesÉrica Leandro Marciano VieiraBruno Mendes RoattDaniel Menezes SouzaMariana Costa DuarteAntônio Lucio Teixeira JuniorLuiz Ricardo Goulart FilhoEduardo Antônio Ferraz Coelhoapplication/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/1843/56622/1/License.txtfa505098d172de0bc8864fc1287ffe22MD51ORIGINALSelection strategy of phage-displayed immunogens based on an in vitro evaluation of the Th1 response of PBMCs and their potential use as a vaccine against leishmania infantum infection.pdfSelection strategy of phage-displayed immunogens based on an in vitro evaluation of the Th1 response of PBMCs and their potential use as a vaccine against leishmania infantum infection.pdfapplication/pdf989270https://repositorio.ufmg.br/bitstream/1843/56622/2/Selection%20strategy%20of%20phage-displayed%20immunogens%20based%20on%20an%20in%20vitro%20evaluation%20of%20the%20Th1%20response%20of%20PBMCs%20and%20their%20potential%20use%20as%20a%20vaccine%20against%20leishmania%20infantum%20infection.pdf1b8d9c10d98c602bab635aa6903f1ea0MD521843/566222023-07-18 17:08:13.416oai:repositorio.ufmg.br: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Repositório de PublicaçõesPUBhttps://repositorio.ufmg.br/oaiopendoar:2023-07-18T20:08:13Repositório Institucional da UFMG - Universidade Federal de Minas Gerais (UFMG)false |
dc.title.pt_BR.fl_str_mv |
Selection strategy of phage-displayed immunogens based on an in vitro evaluation of the Th1 response of PBMCs and their potential use as a vaccine against leishmania infantum infection |
dc.title.alternative.pt_BR.fl_str_mv |
Estratégia de seleção de imunógenos exibidos em fagos com base em uma avaliação in vitro da resposta Th1 de PBMCs e seu potencial uso como vacina contra a infecção por leishmania infantum |
title |
Selection strategy of phage-displayed immunogens based on an in vitro evaluation of the Th1 response of PBMCs and their potential use as a vaccine against leishmania infantum infection |
spellingShingle |
Selection strategy of phage-displayed immunogens based on an in vitro evaluation of the Th1 response of PBMCs and their potential use as a vaccine against leishmania infantum infection Fernanda Fonseca Ramos Phage display Peripheral blood mononuclear cells Immune response Vaccine Visceral leishmaniasis Leishmania infantum Leishmaniose visceral Leishmania infantum Vacinas Técnicas de visualização da superfície celular Imunidade Leucócitos mononucleares |
title_short |
Selection strategy of phage-displayed immunogens based on an in vitro evaluation of the Th1 response of PBMCs and their potential use as a vaccine against leishmania infantum infection |
title_full |
Selection strategy of phage-displayed immunogens based on an in vitro evaluation of the Th1 response of PBMCs and their potential use as a vaccine against leishmania infantum infection |
title_fullStr |
Selection strategy of phage-displayed immunogens based on an in vitro evaluation of the Th1 response of PBMCs and their potential use as a vaccine against leishmania infantum infection |
title_full_unstemmed |
Selection strategy of phage-displayed immunogens based on an in vitro evaluation of the Th1 response of PBMCs and their potential use as a vaccine against leishmania infantum infection |
title_sort |
Selection strategy of phage-displayed immunogens based on an in vitro evaluation of the Th1 response of PBMCs and their potential use as a vaccine against leishmania infantum infection |
author |
Fernanda Fonseca Ramos |
author_facet |
Fernanda Fonseca Ramos Lourena Emanuele Costa Daniel Silva Dias Thaís Teodoro de Oliveira Santos Marcella Rezende Rodrigues Daniela Pagliara Lage Beatriz Cristina Silveira Salles Vívian Tamietti Martins Patrícia Aparecida Fernandes Ribeiro Miguel Angel Chávez Fumagalli Ana Carolina Silva Dias Patrícia Terra Alves Érica Leandro Marciano Vieira Bruno Mendes Roatt Daniel Menezes Souza Mariana Costa Duarte Antônio Lucio Teixeira Junior Luiz Ricardo Goulart Filho Eduardo Antônio Ferraz Coelho |
author_role |
author |
author2 |
Lourena Emanuele Costa Daniel Silva Dias Thaís Teodoro de Oliveira Santos Marcella Rezende Rodrigues Daniela Pagliara Lage Beatriz Cristina Silveira Salles Vívian Tamietti Martins Patrícia Aparecida Fernandes Ribeiro Miguel Angel Chávez Fumagalli Ana Carolina Silva Dias Patrícia Terra Alves Érica Leandro Marciano Vieira Bruno Mendes Roatt Daniel Menezes Souza Mariana Costa Duarte Antônio Lucio Teixeira Junior Luiz Ricardo Goulart Filho Eduardo Antônio Ferraz Coelho |
author2_role |
author author author author author author author author author author author author author author author author author author |
dc.contributor.author.fl_str_mv |
Fernanda Fonseca Ramos Lourena Emanuele Costa Daniel Silva Dias Thaís Teodoro de Oliveira Santos Marcella Rezende Rodrigues Daniela Pagliara Lage Beatriz Cristina Silveira Salles Vívian Tamietti Martins Patrícia Aparecida Fernandes Ribeiro Miguel Angel Chávez Fumagalli Ana Carolina Silva Dias Patrícia Terra Alves Érica Leandro Marciano Vieira Bruno Mendes Roatt Daniel Menezes Souza Mariana Costa Duarte Antônio Lucio Teixeira Junior Luiz Ricardo Goulart Filho Eduardo Antônio Ferraz Coelho |
dc.subject.por.fl_str_mv |
Phage display Peripheral blood mononuclear cells Immune response Vaccine Visceral leishmaniasis Leishmania infantum |
topic |
Phage display Peripheral blood mononuclear cells Immune response Vaccine Visceral leishmaniasis Leishmania infantum Leishmaniose visceral Leishmania infantum Vacinas Técnicas de visualização da superfície celular Imunidade Leucócitos mononucleares |
dc.subject.other.pt_BR.fl_str_mv |
Leishmaniose visceral Leishmania infantum Vacinas Técnicas de visualização da superfície celular Imunidade Leucócitos mononucleares |
description |
Background: The development of a vaccine for the prevention of visceral leishmaniasis (VL) still represents a significant unmet medical need. A human vaccine can be found if one takes into consideration that many people living in endemic areas of disease are infected but do not develop active VL, including those subjects with subclinical or asymptomatic infection. Methods: In this study, a phage display was used to select phage-exposed peptides that were specific to immunoglobulin G (IgG) antibodies from asymptomatic and symptomatic VL patients, separating them from non-infected subjects. Phage clones presenting valid peptide sequences were selected and used as stimuli of peripheral blood mononuclear cells (PBMCs) obtained from both patients’ groups and controls. Those with higher interferon-gamma (IFN-γ)/interleukin (IL)-10 ratios were further selected for vaccination tests. Results: Among 17 evaluated clones, two were selected, B1 and D11, and used to immunize BALB/c mice in an attempt to further validate their in vivo protective efficacy against Leishmania infantum infection. Both clones induced partial protection against the parasite challenge, which was evidenced by the reduction of parasitism in the evaluated organs, a process mediated by a specific T helper (Th)1 immune response. Conclusions: To the best of our knowledge, this study is the first to use a rational strategy based on in vitro stimulation of human PBMCs with selected phage-displayed clones to obtain new immunogens against VL. |
publishDate |
2017 |
dc.date.issued.fl_str_mv |
2017 |
dc.date.accessioned.fl_str_mv |
2023-07-18T20:08:13Z |
dc.date.available.fl_str_mv |
2023-07-18T20:08:13Z |
dc.type.status.fl_str_mv |
info:eu-repo/semantics/publishedVersion |
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info:eu-repo/semantics/article |
format |
article |
status_str |
publishedVersion |
dc.identifier.uri.fl_str_mv |
http://hdl.handle.net/1843/56622 |
dc.identifier.doi.pt_BR.fl_str_mv |
https://doi.org/10.1186/s13071-017-2576-8 |
dc.identifier.issn.pt_BR.fl_str_mv |
1756-3305 |
dc.identifier.orcid.pt_BR.fl_str_mv |
https://orcid.org/0000-0002-7852-0300 https://orcid.org/0000-0001-6129-1719 https://orcid.org/0000-0003-4807-0457 https://orcid.org/0000-0002-8710-9265 https://orcid.org/0000-0002-3100-0009 https://orcid.org/0000-0002-6681-9014 https://orcid.org/0000-0002-6285-8163 https://orcid.org/0000-0002-4147-5614 https://orcid.org/0000-0001-5281-3263 https://orcid.org/0000-0002-9621-5422 https://orcid.org/0000-0002-1803-4861 https://orcid.org/0000-0002-6681-9014 |
url |
https://doi.org/10.1186/s13071-017-2576-8 http://hdl.handle.net/1843/56622 https://orcid.org/0000-0002-7852-0300 https://orcid.org/0000-0001-6129-1719 https://orcid.org/0000-0003-4807-0457 https://orcid.org/0000-0002-8710-9265 https://orcid.org/0000-0002-3100-0009 https://orcid.org/0000-0002-6681-9014 https://orcid.org/0000-0002-6285-8163 https://orcid.org/0000-0002-4147-5614 https://orcid.org/0000-0001-5281-3263 https://orcid.org/0000-0002-9621-5422 https://orcid.org/0000-0002-1803-4861 |
identifier_str_mv |
1756-3305 |
dc.language.iso.fl_str_mv |
eng |
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eng |
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Parasites & Vectors |
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info:eu-repo/semantics/openAccess |
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openAccess |
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Universidade Federal de Minas Gerais |
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UFMG |
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Brasil |
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COLTEC - COLEGIO TECNICO |
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Universidade Federal de Minas Gerais |
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