Forum for Science, Industry and Business

Sponsored by:     3M 
Search our Site:


Novel Antitoxin Strategy Developed Using “Tagged Binding Agents”

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:

More articles from Life Sciences:

nachricht Novel mechanisms of action discovered for the skin cancer medication Imiquimod
21.10.2016 | Technische Universität München

nachricht Second research flight into zero gravity
21.10.2016 | Universität Zürich

All articles from Life Sciences >>>

The most recent press releases about innovation >>>

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

Im Focus: New 3-D wiring technique brings scalable quantum computers closer to reality

Researchers from the Institute for Quantum Computing (IQC) at the University of Waterloo led the development of a new extensible wiring technique capable of controlling superconducting quantum bits, representing a significant step towards to the realization of a scalable quantum computer.

"The quantum socket is a wiring method that uses three-dimensional wires based on spring-loaded pins to address individual qubits," said Jeremy Béjanin, a PhD...

Im Focus: Scientists develop a semiconductor nanocomposite material that moves in response to light

In a paper in Scientific Reports, a research team at Worcester Polytechnic Institute describes a novel light-activated phenomenon that could become the basis for applications as diverse as microscopic robotic grippers and more efficient solar cells.

A research team at Worcester Polytechnic Institute (WPI) has developed a revolutionary, light-activated semiconductor nanocomposite material that can be used...

Im Focus: Diamonds aren't forever: Sandia, Harvard team create first quantum computer bridge

By forcefully embedding two silicon atoms in a diamond matrix, Sandia researchers have demonstrated for the first time on a single chip all the components needed to create a quantum bridge to link quantum computers together.

"People have already built small quantum computers," says Sandia researcher Ryan Camacho. "Maybe the first useful one won't be a single giant quantum computer...

Im Focus: New Products - Highlights of COMPAMED 2016

COMPAMED has become the leading international marketplace for suppliers of medical manufacturing. The trade fair, which takes place every November and is co-located to MEDICA in Dusseldorf, has been steadily growing over the past years and shows that medical technology remains a rapidly growing market.

In 2016, the joint pavilion by the IVAM Microtechnology Network, the Product Market “High-tech for Medical Devices”, will be located in Hall 8a again and will...

Im Focus: Ultra-thin ferroelectric material for next-generation electronics

'Ferroelectric' materials can switch between different states of electrical polarization in response to an external electric field. This flexibility means they show promise for many applications, for example in electronic devices and computer memory. Current ferroelectric materials are highly valued for their thermal and chemical stability and rapid electro-mechanical responses, but creating a material that is scalable down to the tiny sizes needed for technologies like silicon-based semiconductors (Si-based CMOS) has proven challenging.

Now, Hiroshi Funakubo and co-workers at the Tokyo Institute of Technology, in collaboration with researchers across Japan, have conducted experiments to...

All Focus news of the innovation-report >>>



Event News

#IC2S2: When Social Science meets Computer Science - GESIS will host the IC2S2 conference 2017

14.10.2016 | Event News

Agricultural Trade Developments and Potentials in Central Asia and the South Caucasus

14.10.2016 | Event News

World Health Summit – Day Three: A Call to Action

12.10.2016 | Event News

Latest News

Resolving the mystery of preeclampsia

21.10.2016 | Health and Medicine

Stanford researchers create new special-purpose computer that may someday save us billions

21.10.2016 | Information Technology

From ancient fossils to future cars

21.10.2016 | Materials Sciences

More VideoLinks >>>