Safety and Pharmacokinetics of Chimeric Anti-Shiga Toxin 1 and Anti-Shiga Toxin 2 Monoclonal Antibodies in Healthy Volunteers

Bitzan, Martin; Poole, Ruth; Mehran, M.; Sicard, Étienne; Brockus, Catherine; Thuning-Roberson, Claire; Rivière, Marc

doi:10.1128/aac.01661-08

Cited by 87 publications

(59 citation statements)

References 26 publications

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“…Similarly, phase 1 clinical trials of chimeric monoclonal Stx1-and Stx2-neutralizing antibodies were also shown to be generally well tolerated in injected volunteers (383,384). Alternatively, short peptides may block Stx2 transport through epithelial cells (385).…”

Section: Clinical Considerationsmentioning

confidence: 99%

Recent Advances in Understanding Enteric Pathogenic Escherichia coli

et al. 2013

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SUMMARY Although Escherichia coli can be an innocuous resident of the gastrointestinal tract, it also has the pathogenic capacity to cause significant diarrheal and extraintestinal diseases. Pathogenic variants of E. coli (pathovars or pathotypes) cause much morbidity and mortality worldwide. Consequently, pathogenic E. coli is widely studied in humans, animals, food, and the environment. While there are many common features that these pathotypes employ to colonize the intestinal mucosa and cause disease, the course, onset, and complications vary significantly. Outbreaks are common in developed and developing countries, and they sometimes have fatal consequences. Many of these pathotypes are a major public health concern as they have low infectious doses and are transmitted through ubiquitous mediums, including food and water. The seriousness of pathogenic E. coli is exemplified by dedicated national and international surveillance programs that monitor and track outbreaks; unfortunately, this surveillance is often lacking in developing countries. While not all pathotypes carry the same public health profile, they all carry an enormous potential to cause disease and continue to present challenges to human health. This comprehensive review highlights recent advances in our understanding of the intestinal pathotypes of E. coli .

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Section: Clinical Considerationsmentioning

confidence: 99%

Recent Advances in Understanding Enteric Pathogenic Escherichia coli

et al. 2013

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“…59 Blocking the effect of blood-borne STX with inactivating antibodies has also been attempted, and, currently, a trial with monoclonal anti-STX1 and anti-STX2 antibodies is taking place in South America. 64,65 Nevertheless, the main challenge with STX binding and blocking agents has been timing of administration, which needs to occur before the STX effect is further amplified by a cascade of events involving the thrombotic, inflammatory, and complement systems. 59,66 Complement system…”

Section: Shiga Toxin Binding and Blocking Agentsmentioning

confidence: 99%

Management of hemolytic-uremic syndrome in children

Grisaru¹

2014

IJNRD

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Acute renal failure associated with a fulminant, life-threatening systemic disease is rare in previously healthy young children; however, when it occurs, the most common cause is hemolytic-uremic syndrome (HUS). In most cases (90%), this abrupt and devastating illness is a result of ingestion of food or drink contaminated with pathogens that produce very potent toxins. Currently, there are no proven treatment options that can directly inactivate the toxin or effectively interfere with the cascade of destructive events triggered by the toxin once it gains access to the bloodstream and binds its receptor. However, HUS is self-limited, and effective supportive management during the acute phase is proven to be a life saver for children affected by HUS. A minority of childhood HUS cases, approximately 5%, are caused by various genetic mutations causing uncontrolled activation of the complement system. These children, who used to have a poor prognosis leading to end-stage renal disease, now have access to exciting new treatment options that can preserve kidney function and avoid disease recurrences. This review provides a summary of the current knowledge on the epidemiology, pathophysiology, and clinical presentation of childhood HUS, focusing on a practical approach to best management measures.

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“…MAbs targeting protein toxins have demonstrated success in a range of bacterial infections, including infections caused by Clostridium difficile (31), Bacillus anthracis (32,33), and Shiga toxinproducing Escherichia coli (STEC) (34,35), whereby blocking the toxin action prevented pathogenesis. However, targeting the bacterium itself, with its complex pathogenesis, has been a significant hurdle for immunoprevention.…”

Section: Discussionmentioning

confidence: 99%

Targeting Pili in Enterococcal Pathogenesis

et al. 2014

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cPassive protection, the administration of antibodies to prevent infection, has garnered significant interest in recent years as a potential prophylactic countermeasure to decrease the prevalence of hospital-acquired infections. Pili, polymerized protein structures covalently anchored to the peptidoglycan wall of many Gram-positive pathogens, are ideal targets for antibody intervention, given their importance in establishing infection and their accessibility to antibody interactions. In this work, we demonstrated that a monoclonal antibody to the major component of Enterococcus faecalis pili, EbpC, labels polymerized pilus structures, diminishes biofilm formation, and significantly prevents the establishment of a rat endocarditis infection. The effectiveness of this anti-EbpC monoclonal provides strong evidence in support of its potential as a preventative. In addition, after radiolabeling, this monoclonal identified the site of enterococcal infection, providing a rare example of molecularly specific imaging of an established bacterial infection and demonstrating the versatility of this agent for use in future diagnostic and therapeutic applications.

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Safety and Pharmacokinetics of Chimeric Anti-Shiga Toxin 1 and Anti-Shiga Toxin 2 Monoclonal Antibodies in Healthy Volunteers

Abstract: Shiga toxin (Stx)-producing Escherichia coli (STEC) causes hemorrhagic colitis and hemolytic-uremic syndrome (HUS).

Cited by 87 publications

References 26 publications

Recent Advances in Understanding Enteric Pathogenic Escherichia coli

Recent Advances in Understanding Enteric Pathogenic Escherichia coli

Management of hemolytic-uremic syndrome in children

Targeting Pili in Enterococcal Pathogenesis

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