The deleterious effects of Shiga toxin type 2 are neutralized in vitro by fabF8:Stx2 recombinant monoclonal antibody

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dc.contributorLab. Bacteriologiapt_BR
dc.contributorIniciação Científicapt_BR
dc.contributor(BCA) Lab. Biofármacospt_BR
dc.contributorPrograma de Pós-Graduação em Ciências – Toxinologia (PPGTox)pt_BR
dc.contributor.authorLuz, Danielapt_BR
dc.contributor.authorGómez, Fernando D.pt_BR
dc.contributor.authorFerreira, Raissa Lozzardopt_BR
dc.contributor.authorMelo, Bruna de Sousapt_BR
dc.contributor.authorGuth, Beatriz E. C.pt_BR
dc.contributor.authorQuintilio, Wagnerpt_BR
dc.contributor.authorMoro, Ana Mariapt_BR
dc.contributor.authorPresta, Agostinapt_BR
dc.contributor.authorSacerdoti, Flaviapt_BR
dc.contributor.authorIbarra, Cristinapt_BR
dc.contributor.authorChen, Gangpt_BR
dc.contributor.authorSidhu, Sachdev S.pt_BR
dc.contributor.authorAmaral, María Martapt_BR
dc.contributor.authorPiazza, Roxane Maria Fontespt_BR
dc.date.accessioned2021-12-07T15:19:16Z-
dc.date.available2021-12-07T15:19:16Z-
dc.date.issued2021pt_BR
dc.identifier.citationLuz D, Gómez FD., Ferreira RL, Melo BS, Guth BE.C., Quintilio W, et al. The deleterious effects of Shiga toxin type 2 are neutralized in vitro by fabF8:Stx2 recombinant monoclonal antibody. Toxins. 2021 Nov;13(11):825. doi:10.3390/toxins13110825.pt_BR
dc.identifier.urihttps://repositorio.butantan.gov.br/handle/butantan/4009-
dc.description.abstractHemolytic Uremic Syndrome (HUS) associated with Shiga-toxigenic Escherichia coli (STEC) infections is the principal cause of acute renal injury in pediatric age groups. Shiga toxin type 2 (Stx2) has in vitro cytotoxic effects on kidney cells, including human glomerular endothelial (HGEC) and Vero cells. Neither a licensed vaccine nor effective therapy for HUS is available for humans. Recombinant antibodies against Stx2, produced in bacteria, appeared as the utmost tool to prevent HUS. Therefore, in this work, a recombinant FabF8:Stx2 was selected from a human Fab antibody library by phage display, characterized, and analyzed for its ability to neutralize the Stx activity from different STEC-Stx2 and Stx1/Stx2 producing strains in a gold standard Vero cell assay, and the Stx2 cytotoxic effects on primary cultures of HGEC. This recombinant Fab showed a dissociation constant of 13.8 nM and a half maximum effective concentration (EC50) of 160 ng/mL to Stx2. Additionally, FabF8:Stx2 neutralized, in different percentages, the cytotoxic effects of Stx2 and Stx1/2 from different STEC strains on Vero cells. Moreover, it significantly prevented the deleterious effects of Stx2 in a dose-dependent manner (up to 83%) in HGEC and protected this cell up to 90% from apoptosis and necrosis. Therefore, this novel and simple anti-Stx2 biomolecule will allow further investigation as a new therapeutic option that could improve STEC and HUS patient outcomes.pt_BR
dc.description.sponsorship(FAPESP) Fundação de Amparo à Pesquisa do Estado de São Paulopt_BR
dc.description.sponsorshipNational Agency for the Promotion of Science and Technologypt_BR
dc.description.sponsorship(UBA) Universidad de Buenos Airespt_BR
dc.description.sponsorship(CONICET) National Scientific and Technical Research Councilpt_BR
dc.description.sponsorship(CNPq) Conselho Nacional de Desenvolvimento Científico e Tecnológicopt_BR
dc.format.extent825pt_BR
dc.language.isoEnglishpt_BR
dc.relation.ispartofToxinspt_BR
dc.rightsOpen accesspt_BR
dc.rights.urihttps://creativecommons.org/licenses/by/4.0/pt_BR
dc.titleThe deleterious effects of Shiga toxin type 2 are neutralized in vitro by fabF8:Stx2 recombinant monoclonal antibodypt_BR
dc.typeArticlept_BR
dc.rights.licenseCC BYpt_BR
dc.identifier.doi10.3390/toxins13110825pt_BR
dc.identifier.urlhttps://doi.org/10.3390/toxins13110825pt_BR
dc.contributor.external(UBA) Universidad de Buenos Airespt_BR
dc.contributor.external(UNIFESP) Universidade Federal de São Paulopt_BR
dc.contributor.externalUniversity of Torontopt_BR
dc.identifier.citationvolume13pt_BR
dc.identifier.citationissue11pt_BR
dc.subject.keywordSTECpt_BR
dc.subject.keywordStx2pt_BR
dc.subject.keywordantibody fragmentpt_BR
dc.subject.keywordmonoclonal antibodypt_BR
dc.relation.ispartofabbreviatedToxinspt_BR
dc.identifier.citationabntv. 13, n. 11, 825, nov. 2021pt_BR
dc.identifier.citationvancouver2021 Nov;13(11):825pt_BR
dc.contributor.butantanLuz, Daniela|:Técnico|:Lab. Bacteriologia|:PrimeiroAutor|:pt_BR
dc.contributor.butantanFerreira, Raissa Lozzardo|:Aluno egresso|:Lab. Bacteriologia|:Iniciação Científica|:pt_BR
dc.contributor.butantanMelo, Bruna de Sousa|:Aluno Egresso|:Lab. Bacteriologia|:Programa de Pós-Graduação em Ciências – Toxinologia (PPGTox)|:pt_BR
dc.contributor.butantanQuintilio, Wagner|:Pesquisador|:Lab. Biofármacos|:pt_BR
dc.contributor.butantanMoro, Ana Maria|:Pesquisador|:Lab. Biofármacos|:pt_BR
dc.contributor.butantanPiazza, Roxane Maria Fontes|:Pesquisador|:Docente Permanente PPGTox|:Lab. Bacteriologia|:Autor de correspondência|:pt_BR
dc.sponsorship.butantanFundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)¦¦2015/17178-2pt_BR
dc.sponsorship.butantanFundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)¦¦2018/13895-0pt_BR
dc.sponsorship.butantanFundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)¦¦2013/03160-9pt_BR
dc.sponsorship.butantanFundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)¦¦2019/24276-1pt_BR
dc.sponsorship.butantanFundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)¦¦2018/24659-5pt_BR
dc.sponsorship.butantanNational Agency for the Promotion of Science and Technology¦¦ANPCYT-PICT 2017-0617pt_BR
dc.sponsorship.butantanUniversidad de Buenos Aires (UBA)¦¦UBACYT-20020170200154BApt_BR
dc.sponsorship.butantanUniversidad de Buenos Aires (UBA)¦¦UBACYT-20020170100600BApt_BR
dc.sponsorship.butantanNational Scientific and Technical Research Council (CONICET))¦¦PUE 0041pt_BR
dc.sponsorship.butantanFundação Butantan¦¦pt_BR
dc.sponsorship.butantanConselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq)¦¦303969/2017-2pt_BR
dc.sponsorship.butantanConselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq)¦¦307045/2020-0pt_BR
dc.identifier.bvsccBR78.1pt_BR
dc.identifier.bvsdbIBProdpt_BR
dc.description.dbindexedYespt_BR
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