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Toxins 2018, 10(12), 508; https://doi.org/10.3390/toxins10120508

Human Recombinant Fab Fragment Neutralizes Shiga Toxin Type 2 Cytotoxic Effects in vitro and in vivo

1
Laboratório de Bacteriologia, Instituto Butantan, São Paulo 05503900, Brasil
2
Laboratorio de Fisiopatogenia, Departamento de Fisiología, Instituto de Fisiología y Biofísica Bernardo Houssay (IFIBIO Houssay-CONICET), Facultad de Medicina, Universidad de Buenos Aires, Buenos Aires C1121, Argentina
3
Laboratorio de Patogénesis e Inmunología de Procesos Infecciosos, Instituto de Medicina Experimental, (IMEX)-CONICET-Academia Nacional de Medicina, Buenos Aires C1425, Argentina
4
Laboratório de Biofármacos em Células Animais, Instituto Butantan, São Paulo, SP 05503-900, Brazil
These authors contributed equally to this paper.
*
Authors to whom correspondence should be addressed.
Received: 25 September 2018 / Revised: 24 November 2018 / Accepted: 28 November 2018 / Published: 2 December 2018
(This article belongs to the Collection Shiga Toxins)
Full-Text   |   PDF [2196 KB, uploaded 2 December 2018]   |  

Abstract

Shiga toxin (Stx) producing Escherichia coli (STEC) is responsible for causing hemolytic uremic syndrome (HUS), a life-threatening thrombotic microangiopathy characterized by thrombocytopenia, hemolytic anemia, and acute renal failure after bacterially induced hemorrhagic diarrhea. Until now, there has been neither an effective treatment nor method of prevention for the deleterious effects caused by Stx intoxication. Antibodies are well recognized as affinity components of therapeutic drugs; thus, a previously obtained recombinant human FabC11:Stx2 fragment was used to neutralize Stx2 in vitro in a Vero cell viability assay. Herein, we demonstrated that this fragment neutralized, in a dose-dependent manner, the cytotoxic effects of Stx2 on human glomerular endothelial cells, on human proximal tubular epithelial cells, and prevented the morphological alterations induced by Stx2. FabC11:Stx2 protected mice from a lethal dose of Stx2 by toxin-antibody pre-incubation. Altogether, our results show the ability of a new encouraging molecule to prevent Stx-intoxication symptoms during STEC infection. View Full-Text
Keywords: Shiga toxin; recombinant antibody fragment; Fab; neutralization; protection Shiga toxin; recombinant antibody fragment; Fab; neutralization; protection
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Luz, D.; Amaral, M.M.; Sacerdoti, F.; Bernal, A.M.; Quintilio, W.; Moro, A.M.; Palermo, M.S.; Ibarra, C.; Piazza, R.M.F. Human Recombinant Fab Fragment Neutralizes Shiga Toxin Type 2 Cytotoxic Effects in vitro and in vivo. Toxins 2018, 10, 508.

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