Optimizing PEGylation for enhanced formulation of a bacterially-expressed anti-shiga toxin fab fragment for therapeutic use

• Grant number: 25/08038-4
• Support Opportunities: Scholarships abroad - Research Internship - Doctorate
• Start date: July 31, 2025
• End date: January 30, 2026
• Field of knowledge: Health Sciences - Collective Health - Public Health
• Principal Investigator: Daniela Luz Hessel da Cunha
• Grantee: Ariela de Oliveira Pedro Bom Guilherme
• Supervisor: Paul Anthony Dalby
• Host Institution: Instituto Butantan. Secretaria da Saúde (São Paulo - Estado). São Paulo , SP, Brazil
• Institution abroad: University College London (UCL), England
• Associated to the scholarship: 22/11989-2 - Study of the most efficient therapeutic formulation using recombinant Fab antibodies against Shiga toxins (Stx) in in vitro and in vivo models, BP.DR

Abstract

Shiga toxins (Stx), produced by Escherichia coli (STEC), are potent AB5 cytotoxins associated with hemolytic uremic syndrome (HUS), a severe condition characterized by thrombocytopenia, hemolytic anemia, and renal failure, which can be fatal. Currently, no effective therapies exist for Stx-mediated HUS, and antibiotic treatment, particularly quinolones, is not recommended as it induces toxin production and release, worsening the clinical outcome. STEC infections are managed with supportive care only. In this context, Stx neutralization emerges as a promising therapeutic strategy, with antibodies being key tools due to their high specificity and affinity. The objective of the PhD project associated with this proposal is to determine the optimal therapeutic formulation against Stx using PEGylated recombinant Fab antibody fragments targeting Stx1 and Stx2. To achieve this, different Fab-PEG formulations are being tested in vitro and in vivo. Based on the identification of the most effective formulation, the project also aims to improve the PEGylation process and optimize large-scale production in a bacterial expression system. As part of this project, a research internship will be conducted at the Department of Biochemical Engineering at University College London (UCL), in the laboratory of Professor Paul Dalby. The main objective of this internship is to improve the therapeutic formulation and refine the PEGylation process of the most promising anti-Stx Fab candidate, contributing to the advancement of effective treatment strategies for STEC infections. The collaboration with Dr Dalby's group at UCL will expand the possibility to achieve a most promising tool against HUS. (AU)