Human recombinant Fab fragment neutralizes Shiga toxin type 2 cytotoxic effects in vitro and in vivo

DANIELA LUZ; MARIA MARTA AMARAL; FLAVIA SACERDOTI; ALAN MAURO BERNAL; MARINA PALERMO; CRISTINA IBARRA; ROXANE MARIA FONTES PIAZZA

São Paulo

Encuentro; 20ª Reunião Científica Anual do Instituto Butantan "100 anos da Gripe Espanhola - Imagine o Mundo sem Vacinas"; 2018

Instituto Butantan

Shiga toxin (Stx) producing Escherichia coli (STEC) is responsible for causinghemolytic 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.