Human Stx2-Specific Monoclonal Antibodies Prevent Systemic Complications of Escherichia coli O157:H7 Infection

Abstract

Hemolytic-uremic syndrome (HUS) is a serious complication predominantly associated with infection by enterohemorrhagic Escherichia coli (EHEC),

In silico analysis of Shiga toxins (Stxs) to identify new potential vaccine targets for Shiga toxin-producing Escherichia coli

“…Antibiotics therapy is relatively dangerous since it can trigger subsequent bacterial increase and release more stxs that eventually raise the risk of severe clinical complications. Many efforts performed to find protective antigens and develop new vaccine candidates against HUS (Mukherjee et al 2002;Cheng et al 2009). Stxs can directly contribute to the EHEC pathogenesis because they have capability for eliciting protection against EHEC infections by inducing neutralizing antibodies.…”

Transgenèse animale et humanisation des anticorps

“…Ils ont ainsi permis de dériver un certain nombre d'anticorps de forte affinité et d'intérêt commercial important, reconnaissant aussi bien des petites molécules [15], des protéines spécifiques de pathogènes [16,17], des polysaccharides [18], des protéines humaines solubles et des cytokines comme l'interleukine-15 [19][20][21] ou membranaires comme l'antigène spécifique de prostate PSMA, le CD20, le CD30 ou le récepteur à l'EGF (epidermal growth factor) [22][23][24] et des antigènes associés à des tumeurs comme l'antigène carcinoembryonnaire [25]. Les premiers résultats à propos de tous ces Acm semblent très encourageants quant à leur faible immunogé-nicité chez l'homme (➜).…”

Characterization of a Human Monoclonal Antibody against Shiga Toxin 2 Expressed in Chinese Hamster Ovary Cells

“…In contrast, neutralization of the toxin in the blood circulation, close to the organ target, is much more efficient and requires only small quantities of an antitoxin agent, which in the case of antibody, has a relatively long halflife. We have previously reported the production and characterization of human monoclonal antibodies (HuMAbs) against Stx1 and Stx2 (28,29) in transgenic mice which produce fully human antibodies in the absence of mouse antibodies (16,23). These HuMAbs effectively neutralize the cytotoxic effects of the toxins in HeLa cells and are highly protective in both mice and gnotobiotic piglets (14,28,29,46).…”

“…Several therapeutic agents have been developed based on the concept that if the toxin(s) can be absorbed or neutralized in either the gastrointestinal tract or in the circulation, the development of HUS can be prevented. These agents include polymers of trisaccharide of Gb 3 (3,11,12,20,53,58), carbosilane dendrimers with trisaccharides of Gb 3 located at their termini (SUPER TWIG [30]), bacteria with Stx-specific glycolipid receptors (34,35), and Stx-specific antibodies (15,18,28,29,32,37,50). One limitation of most of these therapeutic agents, with the exception of antibodies, is that they are orally administered, which considerably reduces their efficacy.…”

“…We have previously reported the production and characterization of human monoclonal antibodies (HuMAbs) against Stx1 and Stx2 (28,29) in transgenic mice which produce fully human antibodies in the absence of mouse antibodies (16,23). These HuMAbs effectively neutralize the cytotoxic effects of the toxins in HeLa cells and are highly protective in both mice and gnotobiotic piglets (14,28,29,46). The most efficacious of the Stx2-specific HuMAbs are those directed against the A subunit of Stx2, of which 5C12 is the most promising (28).…”