The low-cost, easy-to-replicate tool has demonstrated applications against several different toxins, from those found in contaminated food to those used in bioterrorism, and may also prove effective in targeting other types of pathogens.
The research team, based at Tufts University, demonstrated the method’s efficacy in preventing the symptoms of botulism, a rare but deadly disease caused by Clostridium botulinum neurotoxin (BoNT), considered one of the most dangerous bioterror threat agents.
“Currently, antitoxins are difficult to produce and have a short shelf life, making them very expensive. This new approach provides a low-cost way to develop highly effective antitoxins,” said Doctor Charles B. Shoemaker.
“This method has the potential to target a number of pathogens – not only toxins such as BoNT, but viruses or inflammatory cytokines. It is an important platform through which to address other significant diseases,” says Doctor Saul Tzipori.
Scientists had earlier found that pools of small ‘tagged’ binding agents were highly effective in targeting toxins, neutralising their function, and flagging them for removal via the body’s immune system in the presence of an anti-tag monoclonal antibody.
The researchers have advanced this approach by linking two BoNT-binding agents together and including two copies of the tag. The binding agents are small, stable proteins derived genetically from unusual antibodies produced by toxin-immune alpacas. The resulting molecule, called a ‘double-tagged heterodimer,’ binds to two separate sites on the toxin. Binding of this single heterodimeric agent much more effectively neutralises the toxin than the unlinked monomer binding agents used in the prior research. In addition, attaching two tags to each of the two linked agents leads to toxin decoration by up to four anti-tag monoclonal antibodies, which promotes rapid toxin clearance from the blood, the researchers found.
MEDICA.de; Source: Tufts University