Forum for Science, Industry and Business

Sponsored by:     3M 
Search our Site:

 

Novel Antitoxin Strategy Developed Using “Tagged Binding Agents”

26.02.2010
A study involving the world’s deadliest substance has yielded a new strategy to clear toxins from the body—which may lead to more efficient strategies against toxins that may be used in a bioterrorist event, as well as snake bites, scorpion stings, and even some important chronic diseases.

A Tufts-led team developed the new strategy to deliver small binding agents that seek out Botulinum toxin molecules and bind to them at several points. The binding agents each contain a common “tag” that is recognized by a single, co-administered anti-tag antibody. Once the toxin molecule is surrounded by bound antibodies, it is flushed out of the system through the liver before it can poison the body.

Botulinum toxin, which causes botulism, is the most acutely poisonous substance known and is considered among the most dangerous bioterrorist threats. Studies have shown that one gram of the toxin, which is produced by a bacterium that lives in soil, could kill upwards of a million people. Although currently available antitoxins can be mass produced and delivered in the event of an outbreak, they are costly to develop, house and deliver—and have a short shelf-life.

The Tufts study, in collaboration with researchers at Thomas Jefferson University in Philadelphia, is published this month in the journal Infection and Immunity and was funded by the National Institutes of Allergy and Infectious Diseases (NIAID) and the New England Regional Center for Excellence (NERCE) for Biodefense and Emerging Infectious Diseases.

“We’ve proven this approach to protect against Botulinum intoxication in mice and we hope this will lead to rapid development and deployment of many new anti-toxin therapies—for botulism and beyond,” said Charles B. Shoemaker, PhD, professor of biomedical sciences at Tufts University’s Cummings School of Veterinary Medicine and the study’s corresponding author.

The new findings expand on a 2002 breakthrough at the University of California at San Francisco, where scientists combined three monoclonal antibodies against Botulinum toxin that attached to different parts of the toxin molecule. Including three different antibodies dramatically increased the potency compared to fewer antibodies and prevented intoxication even following high-dose exposure. However, developing, producing, and stockpiling three different monoclonal antibodies against each toxin type is very expensive.

Instead of using three antibodies, the Tufts approach uses three small binding agents to direct a single monoclonal antibody to multiple sites on the biomolecule being targeted for clearance. The type of binding agents used can be selected from many scaffolds developed for commercial therapeutic applications (e.g. nanobodies, aptamers, darpins, FN3, microbodies, etc). These binding agents can be rapidly identified and improved using modern technologies and generally have excellent commercial production and product shelf-life properties. The single anti-tag monoclonal antibody can also be selected to have optimal isotype and commercialization properties.

What’s more, the binding agents can be produced with more than one tag, which enables them to direct more antibodies to the toxin—and synergistically improve target clearance from the body. Many binding agent scaffolds can be produced as functional multimers so that the different binding agents could be produced as “beads on a string,” leading to a single molecule that targets one, or even several, biomolecules for clearance from the body.

Using this approach, the researchers say, one would only need to create new binding agents, not new antibodies, to create a therapy to clear a toxin from the body—paving the way for new therapies that combat toxins ranging from animal venom to bioterrorist agents such as ricin. Tufts researchers are currently targeting Shiga toxin and C. difficile along with other types of Botulinum toxin. Future plans include targeting clearance of pathogenic cytokines that are implicated in inflammation and autoimmune diseases.

Treatment for botulism usually requires many weeks of intensive-care hospitalization, and exposure of even a small number of people would seriously disrupt health care delivery in any major city, studies have indicated. A vaccine has been developed, but widespread use is not currently being considered, the researchers say, since the likelihood of exposure is uncertain. Also, vaccination would block accepted treatments for a number of overactive muscle conditions, including dystonias, which respond to the toxin when administered in very small doses.

The Division of Infectious Diseases at the Cummings School of Veterinary Medicine is Tufts University’s largest research division. In 2003, the division was awarded a $25-million, seven-year contract from the National Institutes of Health (NIH) to develop products to rapidly identify, prevent, treat, and diagnose food and waterborne diseases that threaten public health. Tufts established one of seven national research units within the new national Food and Waterborne Disease Integrated Research Network. The award also launched the Microbiology and Botulism Research Unit, which combines botulism research efforts from Tufts and other public and private institutions in the U.S. and U.K.

The division also oversees the New England Regional Biosafety Laboratory, a 41,000 square foot, level-2 and level-3 facility dedicated to the study of existing and emerging infectious, diseases, toxin-mediated diseases and medical countermeasures important to biodefense.

Cummings School of Veterinary Medicine at Tufts University
Founded in 1978 in North Grafton, Mass., Cummings School of Veterinary Medicine at Tufts University is internationally esteemed for academic programs that impact society and the practice of veterinary medicine; three hospitals and two clinics that combined treat more than 80,000 animals each year; and groundbreaking research that benefits animal, public, and environmental health.

Tom Keppeler | Newswise Science News
Further information:
http://www.tufts.edu

All articles from Life Sciences >>>

The most recent press releases about innovation >>>

Die letzten 5 Focus-News des innovations-reports im Überblick:

Im Focus: Making lightweight construction suitable for series production

More and more automobile companies are focusing on body parts made of carbon fiber reinforced plastics (CFRP). However, manufacturing and repair costs must be further reduced in order to make CFRP more economical in use. Together with the Volkswagen AG and five other partners in the project HolQueSt 3D, the Laser Zentrum Hannover e.V. (LZH) has developed laser processes for the automatic trimming, drilling and repair of three-dimensional components.

Automated manufacturing processes are the basis for ultimately establishing the series production of CFRP components. In the project HolQueSt 3D, the LZH has...

Im Focus: Wonder material? Novel nanotube structure strengthens thin films for flexible electronics

Reflecting the structure of composites found in nature and the ancient world, researchers at the University of Illinois at Urbana-Champaign have synthesized thin carbon nanotube (CNT) textiles that exhibit both high electrical conductivity and a level of toughness that is about fifty times higher than copper films, currently used in electronics.

"The structural robustness of thin metal films has significant importance for the reliable operation of smart skin and flexible electronics including...

Im Focus: Deep inside Galaxy M87

The nearby, giant radio galaxy M87 hosts a supermassive black hole (BH) and is well-known for its bright jet dominating the spectrum over ten orders of magnitude in frequency. Due to its proximity, jet prominence, and the large black hole mass, M87 is the best laboratory for investigating the formation, acceleration, and collimation of relativistic jets. A research team led by Silke Britzen from the Max Planck Institute for Radio Astronomy in Bonn, Germany, has found strong indication for turbulent processes connecting the accretion disk and the jet of that galaxy providing insights into the longstanding problem of the origin of astrophysical jets.

Supermassive black holes form some of the most enigmatic phenomena in astrophysics. Their enormous energy output is supposed to be generated by the...

Im Focus: A Quantum Low Pass for Photons

Physicists in Garching observe novel quantum effect that limits the number of emitted photons.

The probability to find a certain number of photons inside a laser pulse usually corresponds to a classical distribution of independent events, the so-called...

Im Focus: Microprocessors based on a layer of just three atoms

Microprocessors based on atomically thin materials hold the promise of the evolution of traditional processors as well as new applications in the field of flexible electronics. Now, a TU Wien research team led by Thomas Müller has made a breakthrough in this field as part of an ongoing research project.

Two-dimensional materials, or 2D materials for short, are extremely versatile, although – or often more precisely because – they are made up of just one or a...

All Focus news of the innovation-report >>>

Anzeige

Anzeige

Event News

Expert meeting “Health Business Connect” will connect international medical technology companies

20.04.2017 | Event News

Wenn der Computer das Gehirn austrickst

18.04.2017 | Event News

7th International Conference on Crystalline Silicon Photovoltaics in Freiburg on April 3-5, 2017

03.04.2017 | Event News

 
Latest News

DGIST develops 20 times faster biosensor

24.04.2017 | Physics and Astronomy

Nanoimprinted hyperlens array: Paving the way for practical super-resolution imaging

24.04.2017 | Materials Sciences

Atomic-level motion may drive bacteria's ability to evade immune system defenses

24.04.2017 | Life Sciences

VideoLinks
B2B-VideoLinks
More VideoLinks >>>