||

Botulinum

Botulinum neurotoxins (BoNTs) of which there are seven (A-G) distinct serotypes are synthesised by an anaerobic bacterium Clostridium botulinum. These toxins are the most potent known to man. As a comparison of lethality, botulinum toxin is some 10 million times more potent than cyanide on a gram for gram basis. Botulinum toxins serotypes A, B and E and more scarcely F and G are known to be responsible for human cases but all serotypes are listed as potential biological agents in Europe and noted by CDC as potential high risk agents for bioterrorism both due to their toxicity and their ability to be produced and disseminated. Besides deliberate contamination, naturally occurring botulism through food intoxication, or soil contact of wounds, infections are rare but often severe conditions characterised by a progressive descending motor paralysis occur which can be fatal due to paralysis of the respiratory muscle.

 

Currently there are no licensed vaccines against botulism for public use. The only vaccine available for human use is a pentavalent botulinum toxoid vaccine with an IND status, for immunisation of high risk laboratory and military personnel produced by CDC in 1970’s. As part of therapeutic intervention horse derived botulinum antitoxin trivalent is available but such animal sera derived antibodies present serious risk of inducing an intolerance effect and serum sickness.

There are considerable shortfalls in the current prophylactic and therapeutic approach in neutralising toxicity of botulinum toxins. Several strategies are in progress, from production of new vaccines with highly purified toxoids or recombinant portion of toxins, to production of humanised recombinant antibodies.