According to a new study in PLoS One, single domain antibodies found in llamas (sdAb) may help scientists detect botulinum neurotoxins (BoNTs), substances 100 billion times more toxic than cyanide, which the Centers for Disease Control says pose a potential bioterror threat.
The so called "nanobodies" found in llamas are molecularly flexible, unlike conventional antibodies. "As such, sdAb may allow biosensors to be regenerable and used over and over without loss of activity. Also, for some types of BoNT, conventional antibodies are not generally
available and we are filling this biosecurity gap," said Andrew Hayhurst, Ph.D., a virologist with the Southwest Foundation for Biomedical Research. Since some sdAb have been shown to have inhibitory activity and can block toxin function, they may play a role as part of a future anti-botulism treatment.
In the new study, a llama was immunized with harmless versions of seven types of BoNT, blood taken to provide antibody producing cells. Using bioengineering techniques, the antibody genes were cloned and the resulting antibodies were tested for their ability to detect BoNT in selection of drinks, including milk.
BoNTs are made by specific strains of the bacterium Clostridium, which are widely distributed in soils and aquatic sediments. Most cases of botulism are the result of improperly stored foods, which can encourage growth of Clostridia and production of toxin, which is then ingested.
The toxins are extremely potent and target the nervous system, resulting in paralysis that can be so severe as to require life support on a mechanical ventilator for weeks to months. Countermeasures to prevent and treat botulism, such as vaccines and therapeutics, are extremely limited. Consequently, the ability to detect these toxins in the environment is critically important.
"We not only aim to use the antibodies in BoNT detection tests, but also to understand how they bind and inhibit these fascinating molecules," Hayhurst said. "We are also striving to improve our test by making it more sensitive such that one day it may be able to detect much smaller amount of toxins found in patients' blood. Since BoNT also have therapeutic applications with carefully controlled preparations and dosing regimens, there is also an increasing need to monitor BoNT levels in these treatments.
Citation: Conway JO, Sherwood LJ, Collazo MT, Garza JA, Hayhurst A, 'Llama Single Domain Antibodies Specific for the 7 Botulinum Neurotoxin Serotypes as Heptaplex Immunoreagents', PLoS ONE, January 2010 5(1): e8818; doi:10.1371/journal.pone.0008818