Researchers have developed the first oral vaccine against botulism, a bacterial infection that can lead to paralysis and death. The advance, reported in this month's Infection and Immunity, could someday be adapted to make oral vaccines against other diseases, such as diphtheria or tetanus, that plague some developing countries.
While oral vaccines are easier to deliver to patients than injections, it's hard to develop them because most potential vaccines are destroyed by stomach acid. Lance Simpson, a medical professor at Jefferson Medical College in Philadelphia, thought botulism toxin might be an ideal candidate for an oral vaccine. Unlike most proteins, botulism toxin from spoiled canned food, for instance, survives the stomach on its way to its target: nerve cells that control muscles. Once at the nerve endings, the toxin breaks down syntaxin, a protein that directs the release of neurotransmitters. Mice infected with botulism die within 2 hours, and people often die from the infection also.
To detoxify botulism toxin, Simpson mutated the region of the protein that disrupts nerve function, leaving the remainder intact. When he fed the altered protein to mice, they developed antibodies--against both the mutated and natural versions of botulism toxin--that protected the animals from the bug. The vaccine did not harm cultured mouse nerve cells.
Although there is an injected botulism vaccine now in clinical trials, Simpson says his oral vaccine would be easier to administer in developing countries and could also be fed to racehorses and waterfowl species that are prone to botulism (Science, 7 November, p. 1019 ). The botulism toxin might even become a vehicle for delivering other vaccines, Simpson says: "If we can get botulism toxin through the immune system, maybe we can put other proteins on there and create a whole group of oral vaccines."