Botulinum toxins vaccination

Park, J.B. and Simpson, L.L., Inhalational poisoning by botulinum toxin and inhalation vaccination with its heavy-chain component. Infect. Immun., 71, 1147-1154, 2003. 

Botulinum toxin is extremely poisonous to humans. Coats, gloves, face shields, and protective cabinets are recommended for handling botulism specimens. Ideally, laboratory personnel should be vaccinated with C. botulinum antitoxin. Universal precautions should be used when caring for patients suspected of botulism. Isolation is not necessary but droplet precautions should be instituted (Arnon et al., 2001). 

A botulinum toxoid vaccine is made available as an investigational agent through CDC for lab workers who work regularly with botulinum toxin or C. botulinum. Postexposure prophylaxis is not recommended at this time for asymptomatic patients (Arnon et al., 2001). 

The current Centers for Disease Control and Prevention (CDC) therapy for the public is an FDA-approved, bivalent, botulinum equine antitoxin against serotypes A and B. The trivalent antitoxin against types A, B, and E is no longer available. In cases of exposure to any of the other botulinum toxin serotypes, the US Army can provide an investigational heptavalent (ABCDEFG) equine antitoxin, but the time required for typing a toxin subtype would limit its effectiveness in such cases as an outbreak. A parenteral vaccine against the toxin is currently available, but the need exists for newer nonparenteral vaccines that could be administered orally or via inhalation. 

A pentavalent botulinum toxoid (botulinum toxin in different antigenic types) has been used for more than 30 years in some countries to prevent the disease in laboratory workers and to protect troops against attack. Pre-exposure immunization for the general population is neither feasible nor desirable the vaccine is ineffective for postexposure prophylaxis. Treatment of botulism consists of passive immunization and supportive care. Most licensed antitoxins contain antibodies against the most common toxin types A, B, and E. About 9% of recipients of equine antitoxin developed urticaria, serum sickness, or other hypersensitivity reactions. In 2% of recipients anaphylaxis occurred within 10 minutes of antitoxin... 

Chemical Abstracts Service Registry Number CAS 93384-43-1. Botulinum toxins comprise a series of seven related protein neurotoxins that prevent fusion of synaptic vesicles with the presynaptic membrane and thus prevent release of acetylcholine. Exposure in a battlefield or terrorist setting would most likely be to inhaled aerosolized toxin. The clinical presentation is that of classical botulism, with descending skeletal muscle weakness (with an intact sensorium) progressing to respiratory paralysis. A toxoid vaccine is available for prophylaxis, and a pentavalent toxoid can be used following exposure its effectiveness wanes rapidly, however, after the end of the clinically asymptomatic latent period. Because treatment is supportive and intensive (involving long-term ventilatory support), the use of botulinum toxin has the potential to overwhelm medical resources especially at forward echelons of care. 

The currently available toxoid protects against botulinum toxin types A through E, but is available only as an Investigational New Drug/Vaccine product, with the administration of the toxoid controlled by CDC. A series of three vaccinations must be started 12 weeks before exposure. Most recipients show positive evidence of protective titers at 14 weeks, and yearly boosters are required to maintain protection. 

Although more than 3,000 laboratory workers have received the pentavalent vaccine over the past 30 years, it is not administered broadly for several reasons. The toxoid is relatively scarce, expensive, requires several injections, has the side effects described previonsly, and the natnral disease is very rare. The drawbacks of immunizing the entire popnlation clearly outweigh the expense of preventing a very small number of cases. In addition, active immunity to botulinum toxin would preclude the use of the toxin for other medicinal purposes (36). The heptavalent vaccine wonld not be helpfnl postexposure in an ontbreak scenario, because the toxoid requires several injections over several months to induce immunity. A recombinant vaccine, which may overcome these limitations, is in development (36). 

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