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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dc.contributor(LDV) Lab. Desenvolvimento de Vacinaspt_BR
dc.contributorLab. Parasitologiapt_BR
dc.contributorCentro Bioindustrialpt_BR
dc.contributor.authorFarias, Leonardo Paivapt_BR
dc.contributor.authorVitoriano-Souza, Julianapt_BR
dc.contributor.authorCardozo, Lucas Estevespt_BR
dc.contributor.authorGama, Leonardo Dos Reispt_BR
dc.contributor.authorSingh, Youvikapt_BR
dc.contributor.authorMiyasato, Patricia Aokipt_BR
dc.contributor.authorAlmeida, Giulliana Tessarinpt_BR
dc.contributor.authorRodríguez, Duniapt_BR
dc.contributor.authorBarbosa, Mayra Mara Ferraript_BR
dc.contributor.authorFernandes, Rafaela Sachettopt_BR
dc.contributor.authorBarbosa, Tereza Cristinapt_BR
dc.contributor.authorSilva Neto, Almiro Pires dapt_BR
dc.contributor.authorNakano, Elianapt_BR
dc.contributor.authorHo, Paulo Leept_BR
dc.contributor.authorVerjovski-Almeida, Sergiopt_BR
dc.contributor.authorNakaya, Helder Imotopt_BR
dc.contributor.authorWilson, Robert Alanpt_BR
dc.contributor.authorLeite, Luciana Cezar de Cerqueirapt_BR
dc.identifier.citationFarias LP, Vitoriano-Souza J, Cardozo LE, Gama LDR, Singh Y, Miyasato PA, 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. Front. Immunol.. 2021 Mar;12:624191. doi:10.3389/fimmu.2021.624191.pt_BR
dc.description.abstractIn 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-γ; 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.pt_BR
dc.description.sponsorship(FAPESP) Fundação de Amparo à Pesquisa do Estado de São Paulopt_BR
dc.description.sponsorship(CNPq) Conselho Nacional de Desenvolvimento Científico e Tecnológicopt_BR
dc.description.sponsorship(CAPES) Coordenação de Aperfeiçoamento de Pessoal de Nível Superiorpt_BR
dc.relation.ispartofFrontiers in Immunologypt_BR
dc.rightsOpen accesspt_BR
dc.titleSystems biology analysis of the radiation- attenuated schistosome vaccine reveals a role for growth factors in protection and hemostasis inhibition in parasite survivalpt_BR
dc.rights.licenseCC BYpt_BR
dc.contributor.external(FIOCRUZ) Fundação Oswaldo Cruzpt_BR
dc.contributor.external(USP) Universidade de São Paulopt_BR
dc.contributor.externalUniversity of Yorkpt_BR
dc.subject.keywordSchistosoma mansonipt_BR
dc.subject.keywordradiation-attenuated vaccinept_BR
dc.subject.keywordsystems biologypt_BR
dc.subject.keywordimmune responsept_BR
dc.subject.keywordprotection mechanismpt_BR
dc.subject.keywordmouse modelpt_BR
dc.relation.ispartofabbreviatedFront Immunolpt_BR
dc.identifier.citationabntv. 12, 624191, mar. 2021pt_BR
dc.identifier.citationvancouver2021 Mar;12:624191pt_BR
dc.contributor.butantanFarias, Leonardo Paiva|:Aluno|:(LDV) Lab. Desenvolvimento de Vacinas|:PrimeiroAutor:Autor de correspondênciapt_BR
dc.contributor.butantanVitoriano-Souza, Juliana|:Aluno|:(LDV) Lab. Desenvolvimento de Vacinaspt_BR
dc.contributor.butantanMiyasato, Patricia Aoki|:Técnico|:Lab. Parasitologiapt_BR
dc.contributor.butantanAlmeida, Giulliana Tessarin|:Aluno|:Lab. Parasitologiapt_BR
dc.contributor.butantanRodríguez, Dunia|:Pesquisador|:(LDV) Lab. Desenvolvimento de Vacinaspt_BR
dc.contributor.butantanBarbosa, Mayra Mara Ferrari|:Aluno|:(LDV) Lab. Desenvolvimento de Vacinaspt_BR
dc.contributor.butantanFernandes, Rafaela Sachetto|:Aluno|:(LDV) Lab. Desenvolvimento de Vacinaspt_BR
dc.contributor.butantanBarbosa, Tereza Cristina|:Técnico|:(LDV) Lab. Desenvolvimento de Vacinaspt_BR
dc.contributor.butantanNakano, Eliana|:Pesquisador|:Lab. Parasitologiapt_BR
dc.contributor.butantanHo, Paulo Lee|:Pesquisador|:Centro Bioindustrialpt_BR
dc.contributor.butantanVerjovski-Almeida, Sergio|:Pesquisador|:Lab. Parasitologiapt_BR
dc.contributor.butantanLeite, Luciana Cezar de Cerqueira|:Pesquisador|:(LDV) Lab. Desenvolvimento de Vacinas|:Autor de correspondênciapt_BR
dc.sponsorship.butantan(FAPESP) Fundação de Amparo à Pesquisa do Estado de São Paulo¦¦012/23124-4pt_BR
dc.sponsorship.butantan(FAPESP) Fundação de Amparo à Pesquisa do Estado de São Paulo¦¦2012/18095-5pt_BR
dc.sponsorship.butantan(CNPq) Conselho Nacional de Desenvolvimento Científico e Tecnológicopt_BR
dc.sponsorship.butantan(CAPES) Coordenação de Aperfeiçoamento de Pessoal de Nível Superiorpt_BR
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