herapeutic Antibodies Against Shiga Toxins: Trends and Perspective

Author(s)

Henrique, Izabella de Macedo ^[1] ; Sacerdoti, Flavia ^[2] ; Ferreira, Raissa Lozzardo ^[1] ; Henrique, Camila ^[1] ; Amaral, Maria Marta ^[2] ; Piazza, Roxane Maria Fontes ^[1] ; Luz, Daniela ^[1]

Affiliation

^[1] Inst Butantan, Lab Bacteriol, Sao Paulo - Brazil

^[2] Univ Buenos Aires, Lab Fisiopatogenia, Inst Fisiol & Biofis Bernardo Houssay IFIBIO Hous, Dept Fisiol, Fac Med, Buenos Aires, DF - Argentina

• Document type: Review article
• Source: FRONTIERS IN CELLULAR AND INFECTION MICROBIOLOGY; v. 12, FEB 10 2022.
• Web of Science Citations: 0

Abstract

Shiga toxins (Stx) are AB(5)-type toxins, composed of five B subunits which bind to Gb(3) host cell receptors and an active A subunit, whose action on the ribosome leads to protein synthesis suppression. The two Stx types (Stx1 and Stx2) and their subtypes can be produced by Shiga toxin-producing Escherichia coli strains and some Shigella spp. These bacteria colonize the colon and induce diarrhea that may progress to hemorrhagic colitis and in the most severe cases, to hemolytic uremic syndrome, which could lead to death. Since the use of antibiotics in these infections is a topic of great controversy, the treatment remains supportive and there are no specific therapies to ameliorate the course. Therefore, there is an open window for Stx neutralization employing antibodies, which are versatile molecules. Indeed, polyclonal, monoclonal, and recombinant antibodies have been raised and tested in vitro and in vivo assays, showing differences in their neutralizing ability against deleterious effects of Stx. These molecules are in different phases of development for which we decide to present herein an updated report of these antibody molecules, their source, advantages, and disadvantages of the promising ones, as well as the challenges faced until reaching their applicability. (AU)

• 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: 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: 17/17213-8 - Heat Labile (LT) and heat-stable (st) toxins produced by Enterotoxigenic Escherichia coli: study of a new in vivo model for the evaluation of the neutralizing potential of recombinant antibodies
• Grantee: Camila Henrique Pinto
• Support Opportunities: Scholarships in Brazil - Doctorate
• 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
• 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: 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