Systems biology analysis of the radiation-attenuated Schistosome vaccine reveals a role for growth factors in protection and hemostasis inhibition in parasite survival

Farias, Leonardo Paiva; Souza, Juliana Vitoriano; Cardozo, Lucas Esteves; Gama, Leonardo Dos Reis; Singh, Youvika; Miyasato, Patrícia Aoki; Almeida, Giulliana Tessarin; Rodriguez, Dunia; Barbosa, Mayra Mara Ferrari; Fernandes, Rafaela Sachetto; Barbosa, Tereza Cristina; Silva Neto, Almiro Pires da; Nakano, Eliana; Ho, Paulo Lee; Almeida, Sergio Verjovski; Nakaya, Helder Imoto; Wilson, Robert Alan; Leite, Luciana Cezar de Cerqueira

Systems biology analysis of the radiation-attenuated Schistosome vaccine reveals a role for growth factors in protection and hemostasis inhibition in parasite survival

Detalhes bibliográficos
Autor(a) principal:	Farias, Leonardo Paiva
Data de Publicação:	2021
Outros Autores:	Souza, Juliana Vitoriano, Cardozo, Lucas Esteves, Gama, Leonardo Dos Reis, Singh, Youvika, Miyasato, Patrícia Aoki, Almeida, Giulliana Tessarin, Rodriguez, Dunia, Barbosa, Mayra Mara Ferrari, Fernandes, Rafaela Sachetto, Barbosa, Tereza Cristina, Silva Neto, Almiro Pires da, Nakano, Eliana, Ho, Paulo Lee, Almeida, Sergio Verjovski, Nakaya, Helder Imoto, Wilson, Robert Alan, Leite, Luciana Cezar de Cerqueira
Tipo de documento:	Artigo
Idioma:	eng
Título da fonte:	Repositório Institucional da FIOCRUZ (ARCA)
Texto Completo:	https://www.arca.fiocruz.br/handle/icict/47689
Resumo:	Fundação de Amparo à Pesquisa do Estado de São Paulo to LF and LL (2012/23124-4)

Metadados do item

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network_acronym_str	CRUZ
network_name_str	Repositório Institucional da FIOCRUZ (ARCA)
repository_id_str	2135
spelling	Farias, Leonardo PaivaSouza, Juliana VitorianoCardozo, Lucas EstevesGama, Leonardo Dos ReisSingh, YouvikaMiyasato, Patrícia AokiAlmeida, Giulliana TessarinRodriguez, DuniaBarbosa, Mayra Mara FerrariFernandes, Rafaela SachettoBarbosa, Tereza CristinaSilva Neto, Almiro Pires daNakano, ElianaHo, Paulo LeeAlmeida, Sergio VerjovskiNakaya, Helder ImotoWilson, Robert AlanLeite, Luciana Cezar de Cerqueira2021-06-15T14:06:05Z2021-06-15T14:06:05Z2021FARIAS, Leonardo Paiva et al. Systems biology analysis of the radiation-attenuated Schistosome vaccine reveals a role for growth factors in protection and hemostasis inhibition in parasite survival. Frontiers in Immunology, v. 12, p. 1-18, 11 Mar. 2021.1664-3224https://www.arca.fiocruz.br/handle/icict/4768910.3389/fimmu.2021.624191Fundação de Amparo à Pesquisa do Estado de São Paulo to LF and LL (2012/23124-4)Fundação Butantan, and by fellowships from FAPESP to JV-S (2012/18095-5)Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq) to LLCoordenação de Aperfeiçoamento de Pessoal de Nı́vel Superior—Brasil (CAPES)—Finance Code 001 to MFInstituto Butantan. Laboratório de Desenvolvimento de Vacinas. São Paulo, SP, Brasil / Fundação Oswaldo Cruz. Instituto Gonçalo Moniz. Laboratório de Inflamação e Biomarcadores. Salvador, BA, Brasil.Instituto Butantan. Laboratório de Desenvolvimento de Vacinas. São Paulo, SP, Brasil.Universidade de São Paulo. Faculdade de Ciências Farmacêuticas. São Paulo, SP, Brasil.Universidade de São Paulo. Faculdade de Ciências Farmacêuticas. São Paulo, SP, Brasil.Universidade de São Paulo. Faculdade de Ciências Farmacêuticas. São Paulo, SP, Brasil.Instituto Butantan. Laboratório de Parasitologia. São Paulo, SP, Brasil.Instituto Butantan. Laboratório de Parasitologia. São Paulo, SP, Brasil / Universidade de São Paulo. Instituto de Química. São Paulo, SP, Brasil.Instituto Butantan. Laboratório de Desenvolvimento de Vacinas. São Paulo, SP, Brasil.Instituto Butantan. Laboratório de Desenvolvimento de Vacinas. São Paulo, SP, Brasil / Universidade de São Paulo. Programa de Pós-Graduação Interunidades em Biotecnologia. São Paulo, SP, Brasil.Instituto Butantan. Laboratório de Desenvolvimento de Vacinas. São Paulo, SP, Brasil / Universidade de São Paulo. Programa de Pós-Graduação Interunidades em Biotecnologia. São Paulo, SP, Brasil.Instituto Butantan. Laboratório de Desenvolvimento de Vacinas. São Paulo, SP, Brasil.Fundação Oswaldo Cruz. Instituto Gonçalo Moniz. Laboratório de Inflamação e Biomarcadores. Salvador, BA, Brasil.Instituto Butantan. Laboratório de Parasitologia. São Paulo, SP, Brasil.Instituto Butantan. Centro Bioindustrial. São Paulo, SP, Brasil.Instituto Butantan. Laboratório de Parasitologia. São Paulo, SP, Brasil / Universidade de São Paulo. Instituto de Química. São Paulo, SP, Brasil.Universidade de São Paulo. Faculdade de Ciências Farmacêuticas. São Paulo, SP, Brasil.University of York. York Biomedical Research Institute. York, United Kingdom.Instituto Butantan. Laboratório de Desenvolvimento de Vacinas. São Paulo, SP, Brasil.In spite of several decades of research, an effective vaccine against schistosomiasis remains elusive. The radiation-attenuated (RA) cercarial vaccine is still the best model eliciting high protection levels, although the immune mechanisms have not yet been fully characterized. In order to identify genes and pathways underlying protection we investigated patterns of gene expression in PBMC and skin draining Lymph Nodes (LN) from mice using two exposure comparisons: vaccination with 500 attenuated cercariae versus infection with 500 normal cercariae; one versus three doses. Vaccinated mice were challenged with 120 normal parasites. Integration of PBMC and LN data from the infected group revealed early up-regulation of pathways associated with Th2 skewing and polarization of IgG antibody profiles. Additionally, hemostasis pathways were downregulated in infected mice, correlating with platelet reduction, potentially a mechanism to assist parasite migration through capillary beds. Conversely, up regulation of such mechanisms after vaccination may explain parasite blockade in the lungs. In contrast, a single exposure to attenuated parasites revealed early establishment of a Th1 bias (signaling of IL-1, IFN-g; and Leishmania infection). Genes encoding chemokines and their receptors were more prominent in vaccinated mice, indicating an enhanced capacity for inflammation, potentially augmenting the inhibition of intravascular migration. Increasing the vaccinations from one to three did not dramatically elevate protection, but there was a clear shift towards antibody-mediated effectors. However, elements of the Th1 bias were still evident. Notable features after three vaccinations were markers of cytotoxicity (including IL-6 and NK cells) together with growth factors and their receptors (FGFR/VEGF/EGF) and the apoptosis pathway. Indeed, there is evidence for the development of anergy after three vaccinations, borne out by the limited responses detected in samples after challenge. We infer that persistence of a Th1 response puts a limit on expression of antibody-mediated mechanisms. This feature may explain the failure of multiple doses to drive protection towards sterile immunity. We suggest that the secretions of lung stage parasites would make a novel cohort of antigens for testing in protection experiments.engFrontiers MediaSchistosoma mansoniVacinaçãoBiologia de sistemasRadiaçãoProteçãoSchistosoma mansoniRadiation-attenuated vaccineSystems biologyImmune responseProtection mechanismMouse modelSystems biology analysis of the radiation-attenuated Schistosome vaccine reveals a role for growth factors in protection and hemostasis inhibition in parasite survivalinfo:eu-repo/semantics/publishedVersioninfo:eu-repo/semantics/articleinfo:eu-repo/semantics/openAccessreponame:Repositório Institucional da FIOCRUZ (ARCA)instname:Fundação Oswaldo Cruz (FIOCRUZ)instacron:FIOCRUZLICENSElicense.txtlicense.txttext/plain; charset=utf-83097https://www.arca.fiocruz.br/bitstream/icict/47689/1/license.txt36b51ef91c52b5338d9d29ba0cc807bcMD51ORIGINALFarias, Leonardo Paiva Systems....pdfFarias, Leonardo Paiva 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dc.title.pt_BR.fl_str_mv	Systems biology analysis of the radiation-attenuated Schistosome vaccine reveals a role for growth factors in protection and hemostasis inhibition in parasite survival
title	Systems biology analysis of the radiation-attenuated Schistosome vaccine reveals a role for growth factors in protection and hemostasis inhibition in parasite survival
spellingShingle	Systems biology analysis of the radiation-attenuated Schistosome vaccine reveals a role for growth factors in protection and hemostasis inhibition in parasite survival Farias, Leonardo Paiva Schistosoma mansoni Vacinação Biologia de sistemas Radiação Proteção Schistosoma mansoni Radiation-attenuated vaccine Systems biology Immune response Protection mechanism Mouse model
title_short	Systems biology analysis of the radiation-attenuated Schistosome vaccine reveals a role for growth factors in protection and hemostasis inhibition in parasite survival
title_full	Systems biology analysis of the radiation-attenuated Schistosome vaccine reveals a role for growth factors in protection and hemostasis inhibition in parasite survival
title_fullStr	Systems biology analysis of the radiation-attenuated Schistosome vaccine reveals a role for growth factors in protection and hemostasis inhibition in parasite survival
title_full_unstemmed	Systems biology analysis of the radiation-attenuated Schistosome vaccine reveals a role for growth factors in protection and hemostasis inhibition in parasite survival
title_sort	Systems biology analysis of the radiation-attenuated Schistosome vaccine reveals a role for growth factors in protection and hemostasis inhibition in parasite survival
author	Farias, Leonardo Paiva
author_facet	Farias, Leonardo Paiva Souza, Juliana Vitoriano Cardozo, Lucas Esteves Gama, Leonardo Dos Reis Singh, Youvika Miyasato, Patrícia Aoki Almeida, Giulliana Tessarin Rodriguez, Dunia Barbosa, Mayra Mara Ferrari Fernandes, Rafaela Sachetto Barbosa, Tereza Cristina Silva Neto, Almiro Pires da Nakano, Eliana Ho, Paulo Lee Almeida, Sergio Verjovski Nakaya, Helder Imoto Wilson, Robert Alan Leite, Luciana Cezar de Cerqueira
author_role	author
author2	Souza, Juliana Vitoriano Cardozo, Lucas Esteves Gama, Leonardo Dos Reis Singh, Youvika Miyasato, Patrícia Aoki Almeida, Giulliana Tessarin Rodriguez, Dunia Barbosa, Mayra Mara Ferrari Fernandes, Rafaela Sachetto Barbosa, Tereza Cristina Silva Neto, Almiro Pires da Nakano, Eliana Ho, Paulo Lee Almeida, Sergio Verjovski Nakaya, Helder Imoto Wilson, Robert Alan Leite, Luciana Cezar de Cerqueira
author2_role	author author author author author author author author author author author author author author author author author
dc.contributor.author.fl_str_mv	Farias, Leonardo Paiva Souza, Juliana Vitoriano Cardozo, Lucas Esteves Gama, Leonardo Dos Reis Singh, Youvika Miyasato, Patrícia Aoki Almeida, Giulliana Tessarin Rodriguez, Dunia Barbosa, Mayra Mara Ferrari Fernandes, Rafaela Sachetto Barbosa, Tereza Cristina Silva Neto, Almiro Pires da Nakano, Eliana Ho, Paulo Lee Almeida, Sergio Verjovski Nakaya, Helder Imoto Wilson, Robert Alan Leite, Luciana Cezar de Cerqueira
dc.subject.other.pt_BR.fl_str_mv	Schistosoma mansoni Vacinação Biologia de sistemas Radiação Proteção
topic	Schistosoma mansoni Vacinação Biologia de sistemas Radiação Proteção Schistosoma mansoni Radiation-attenuated vaccine Systems biology Immune response Protection mechanism Mouse model
dc.subject.en.en.fl_str_mv	Schistosoma mansoni Radiation-attenuated vaccine Systems biology Immune response Protection mechanism Mouse model
description	Fundação de Amparo à Pesquisa do Estado de São Paulo to LF and LL (2012/23124-4)
publishDate	2021
dc.date.accessioned.fl_str_mv	2021-06-15T14:06:05Z
dc.date.available.fl_str_mv	2021-06-15T14:06:05Z
dc.date.issued.fl_str_mv	2021
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.citation.fl_str_mv	FARIAS, Leonardo Paiva et al. Systems biology analysis of the radiation-attenuated Schistosome vaccine reveals a role for growth factors in protection and hemostasis inhibition in parasite survival. Frontiers in Immunology, v. 12, p. 1-18, 11 Mar. 2021.
dc.identifier.uri.fl_str_mv	https://www.arca.fiocruz.br/handle/icict/47689
dc.identifier.issn.pt_BR.fl_str_mv	1664-3224
dc.identifier.doi.pt_BR.fl_str_mv	10.3389/fimmu.2021.624191
identifier_str_mv	FARIAS, Leonardo Paiva et al. Systems biology analysis of the radiation-attenuated Schistosome vaccine reveals a role for growth factors in protection and hemostasis inhibition in parasite survival. Frontiers in Immunology, v. 12, p. 1-18, 11 Mar. 2021. 1664-3224 10.3389/fimmu.2021.624191
url	https://www.arca.fiocruz.br/handle/icict/47689
dc.language.iso.fl_str_mv	eng
language	eng
dc.rights.driver.fl_str_mv	info:eu-repo/semantics/openAccess
eu_rights_str_mv	openAccess
dc.publisher.none.fl_str_mv	Frontiers Media
publisher.none.fl_str_mv	Frontiers Media
dc.source.none.fl_str_mv	reponame:Repositório Institucional da FIOCRUZ (ARCA) instname:Fundação Oswaldo Cruz (FIOCRUZ) instacron:FIOCRUZ
instname_str	Fundação Oswaldo Cruz (FIOCRUZ)
instacron_str	FIOCRUZ
institution	FIOCRUZ
reponame_str	Repositório Institucional da FIOCRUZ (ARCA)
collection	Repositório Institucional da FIOCRUZ (ARCA)
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repository.name.fl_str_mv	Repositório Institucional da FIOCRUZ (ARCA) - Fundação Oswaldo Cruz (FIOCRUZ)
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Systems biology analysis of the radiation-attenuated Schistosome vaccine reveals a role for growth factors in protection and hemostasis inhibition in parasite survival

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