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(Reference retrieved automatically from Web of Science through information on FAPESP grant and its corresponding number as mentioned in the publication by the authors.)

The Deleterious Effects of Shiga Toxin Type 2 Are Neutralized In Vitro by FabF8:Stx2 Recombinant Monoclonal Antibody

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Author(s):
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Luz, Daniela [1] ; Gomez, Fernando D. [2] ; Ferreira, Raissa L. [1] ; Melo, Bruna S. [1] ; Guth, Beatriz E. C. [3] ; Quintilio, Wagner [4] ; Moro, Ana Maria [4] ; Presta, Agostina [2] ; Sacerdoti, Flavia [2] ; Ibarra, Cristina [2] ; Chen, Gang [5] ; Sidhu, Sachdev S. [5] ; Amaral, Maria Marta [2] ; Piazza, Roxane M. F. [1]
Total Authors: 14
Affiliation:
[1] Inst Butantan, Lab Bacteriol, BR-05503900 Sao Paulo - Brazil
[2] Univ Buenos Aires, Fac Med, Dept Fisiol, Inst Fisiol Biofis Bernardo Houssay IFIBIO Ho, RA-1121 Buenos Aires, DF - Argentina
[3] Univ Fed Sao Paulo, Dept Microbiol Imunol & Parasitol, BR-04023062 Sao Paulo - Brazil
[4] Inst Butantan, Lab Biofarmacos, BR-05503900 Sao Paulo - Brazil
[5] Univ Toronto, Terrence Donnelly Ctr Cellular & Biomol Res, Banting & Best Dept Med Res, Toronto, ON M5S 3E1 - Canada
Total Affiliations: 5
Document type: Journal article
Source: TOXINS; v. 13, n. 11 NOV 2021.
Web of Science Citations: 0
Abstract

Hemolytic 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. (AU)

FAPESP's process: 13/03160-9 - New strategies for recombinant antibodies generation against Stx1 and Stx2 toxins produced by Shiga toxin-producing E. coli
Grantee:Daniela Luz Hessel da Cunha
Support Opportunities: Scholarships abroad - Research Internship - Doctorate
FAPESP's process: 19/24276-1 - Establishing efficient protocols and platforms for the obtainment of monoclonal biosimilar with a commercial interest: recombinant monoclonal antibodies anti-TNFa as a development model
Grantee:Daniela Luz Hessel da Cunha
Support Opportunities: Regular Research Grants
FAPESP's process: 18/24659-5 - In vitro evaluation of the neutralizing capacity in human renal cell lines of recombinant Fab fragments against Shiga toxins
Grantee:Raissa Lozzardo Ferreira
Support Opportunities: Scholarships in Brazil - Scientific Initiation
FAPESP's process: 18/13895-0 - Phage library for generation of recombinant antibodies: novel approaches for diagnosis and therapy of infections caused by different Escherichia coli pathotypes
Grantee:Roxane Maria Fontes Piazza
Support Opportunities: Regular Research Grants
FAPESP's process: 15/17178-2 - OPTIMIZATION AND CHARACTERIZATION OF RECOMBINANT ANTIBODIES AND THEIR APPLICATION FOR DIAGNOSIS AND THERAPY OF SHIGA, HEAT-LABILE AND HEAT-STABLE ENTEROTOXINS
Grantee:Roxane Maria Fontes Piazza
Support Opportunities: Regular Research Grants