Therapeutic Antibodies Against Shiga Toxins: Trends and Perspectives

Abstract

Shiga toxins (Stx) are AB5-type toxins, composed of five B subunits which bind to Gb3 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.

What is the role of microbial biotechnology and genetic engineering in medicine?

“…In contrast, monoclonal antibodies are composed of a single IgG against one epitope (i.e., made using identical immune cells) (Mitra & Tomar, 2021). Monoclonal antibodies allow for higher specificity to (as polyclonal antibodies do) (Henrique et al, 2022). For general research applications, however, the advantages of polyclonal antibodies typically outweigh the few advantages that monoclonal antibodies provide.…”

Diagnosis and Treatment for Shiga Toxin-Producing Escherichia coli Associated Hemolytic Uremic Syndrome

“…Antibodies can neutralize Stxs in the serum and potentially even in the gut, making these molecules powerful weapons against toxins. In order to produce antibodies for therapeutic use, there are three main approaches: polyclonal antibody (pAb) generation by animal immunization; monoclonal antibody (mAb) production for the secretion of mAbs specific to lymphocyte immortalization; and the creation of different recombinant antibody (rAb) forms for different targets through DNA recombination techniques and heterologous expression systems [ 184 ] ( Figure 1 and Figure 3 ). Compared with monoclonal antibodies, polyclonal antibodies (pAbs) have many advantages in antitoxin therapy, including the ability to recognize a large number of epitopes, stronger affinity than monoclonal antibodies, and the ability to recognize variants of toxins to reduce the risk of escape [ 118 , 185 ].…”

“…However, although polyclonal antibodies have shown promising neutralization in vitro and in vivo, animal sources of polyclonal antibodies may induce anti-antibody action that inactivates therapeutic antibodies before they can exert their toxin-neutralizing activity. In addition, the amount of animal serum is limited by the size of the immunized animal [ 184 ]. Equine polyclonal antibodies (EpAbs) are easy to manufacture and have been successfully used in a variety of diseases.…”

Antibody-Based Immunotherapies as a Tool for Tackling Multidrug-Resistant Bacterial Infections

“…Antibodies together with B and T cells constitute one of the most important components of the adaptive immune system. Antibodies or immunoglobulins (Igs) are Y-shaped glycoproteins capable of specifically recognizing antigens, attaching and forming a molecular link in the communication network of the remaining elements of the immune system, activating the complement components of the immune response, and leading to neutralization or elimination of foreign threats [11].…”