Botulinum toxin as a carrier for oral vaccines

Botulinum toxin is an unusually potent substance that acts on the nervous system to produce the clinical outcome of flaccid paralysis. To produce this effect, the toxin ordinarily proceeds through two separate but essential sequences of events. During the first, the toxin is ingested, it traverses a portion of the gastrointestinal system and then it is transcytosed from the lumen of the gut to the general circulation. During the second, circulating toxin binds to peripheral cholinergic nerve endings, it is endocytosed and then it acts as a metalloendoprotease to cleave polypeptides that are essential for exocytosis. Although botulinum toxin is antigenic, it ordinarily does not evoke an immune response during or after cases of oral poisoning. This is due to the fact that the dose of toxin that produces flaccid paralysis-and potentially death-is less than the dose needed to evoke an antibody response. In the recent past, the techniques of molecular biology have been used to generate an expression product of botulinum toxin that retains the ability to escape the gut and reach the general circulation, retains the ability to evoke an immune response, but has lost the ability to produce neurotoxicity. This modified toxin may have two clinical applications. The expression product itself may have utility as an oral vaccine against botulism. Beyond this, the modified toxin, or a truncation mutant of the toxin, may have utility as a carrier in the construction of other oral vaccines. Both potential applications could lead to the expression of oral vaccines in common foods.