Shiga toxin-producing Escherichia coli (STEC), a significant public health concern, can lead to Hemolytic-Uremic Syndrome (HUS). Our company has extensive experience in developing effective STEC-HUS vaccines and therapeutics, with the ultimate goal of providing one-stop solutions to global pharmaceutical companies.
Overview of STEC-Hemolytic-uremic Syndrome
Shiga toxin-producing Escherichia coli (STEC) infections are a major public health concern worldwide, with the potential to cause a severe and life-threatening complication known as Shiga toxin-associated hemolytic-uremic syndrome (STEC-HUS). This condition is characterized by the triad of microangiopathic hemolytic anemia, thrombocytopenia, and acute kidney injury.
The pathogenesis of STEC-HUS involves the production of potent Shiga toxins (Stx1 and Stx2) by certain STEC strains, primarily E. coli O157:H7. These toxins target and damage the endothelial cells lining the blood vessels, leading to platelet activation, thrombus formation, and subsequent organ dysfunction, particularly in the kidneys.
Fig.1 Schematic diagram of STEC-HUS pathogenesis and therapeutic targets. (Liu Y., et al., 2022)
Vaccine Development for STEC-HUS
The development of a vaccine against STEC-HUS is imperative due to the severity of the disease and its potential complications, including chronic kidney disease and neurological impairments. The goal of an STEC-HUS vaccine is to elicit an immune response that prevents the colonization of STEC in the gut and the subsequent release of Shiga toxins.
Current vaccine development strategies include:
- Attenuated Bacteria: Using weakened forms of STEC to stimulate an immune response without causing disease.
- Recombinant Proteins: Developing proteins that mimic parts of the STEC bacteria to induce immunity.
- Polysaccharide Conjugates: Linking sugar molecules to proteins to enhance the immune response, especially in infants and young children.
Therapeutics Development for STEC-HUS
In recent years, alternative therapies targeting Shiga toxins have shown promise. These include:
- Anti-Shiga Toxin Antibodies: Designed to neutralize the toxins in the bloodstream.
- Toxin Receptor Inhibitors: Such as Gb3Cer inhibitors, which block the receptors that Shiga toxins use to enter cells.
- Retro-2: A compound that disrupts the intracellular transport of Shiga toxins, preventing their cytotoxic effects.
Table 1 Clinical trials on the therapeutics of STEC-HUS. (Liu Y., et al., 2022)
Identifier |
Interventions |
Time Period |
Country |
NCT00004465 |
SYNSORB Pk vs. placebo |
1997/7/27~2001/4/14 |
United States, Canada |
SHIGATEC |
Shigamabs(cαStx1/cαStx2) vs. placebo |
2010/11~2011/2 |
Argentina, Chile, Peru |
NCT01252199 |
cαStx1/cαStx2 vs. placebo |
2011/11~2013/2 |
Argentina, Chile, Peru |
NCT01406288 |
HUS standard coverage care (including in ICU) |
2011/7~2012/3 |
France |
NCT01410916 |
Eculizumab (Soliris®) vs. placebo |
2011/7~2012/6 |
Germany |
NCT02205541 |
Eculizumab vs. placebo |
2015/6~2018/6 |
France |
NCT02336516 |
Azithromycin vs. placebo |
2015/7~2021/4 |
France |
ECUSTEC |
Eculizumab vs. placebo |
2016/12~2021/4 |
United Kingdom |
NCT03388216 |
INM004 vs. placebo |
2017/12/16~2018/9/28 |
Argentina |
NCT03776851 |
Erythropoietin (EPO) |
2019/1/1~2020/12/30 |
Argentina |
NCT04132375 |
INM004 vs. placebo |
2019/7/17~2022/9/1 |
Argentina |
NCT05219110 |
Hyperhydration vs. conservative fluid management |
2022/9/1~2027/8/31 |
United States, Canada |
Our Services
At our company, we offer a comprehensive suite of STEC-HUS research services to support the development of both vaccines and therapies. Our state-of-the-art facilities and experienced team of scientists provide the following capabilities:
Infectious Disease Models
- STEC Induced Models
- Purified Stx2 Induced Models
- VTEC/VT2 Induced Models
- VT2 Induced Models
- Purified Stx1 and Stx2a Induced Models
- EHEC O104:H4 Induced Models
- O153/O157:H7 Induced Models
By combining our deep scientific expertise, state-of-the-art facilities, and a strong commitment to innovation, our company is uniquely positioned to accelerate the development of transformative STEC-HUS solutions. If our services have piqued your interest, we warmly welcome you to reach out to us for further information and to obtain a detailed quotation for the services you require.
Reference
- Liu Yang, et al. "Diagnosis and treatment for Shiga toxin-producing Escherichia coli associated hemolytic uremic syndrome." Toxins 15.1 (2022): 10.
All of our services and products are intended for preclinical research use
only and cannot be used to diagnose, treat or manage patients.