Botulinum Vaccine

Trivalent botulinum antitoxin (A,B,E) Horse antibotulism serum (globulin) Botulinum Vaccine... 

A vaccine preparation now available allows an individual to develop antibodies to the five most common C. botulinum types (A, B, C, D, and E). Studies have shown that the vaccine regimen produces protective antitoxin levels in greater than 90% of those vaccinated.3... 

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. 

However, severe constraints do exist on DoD use of IND drugs and vaccines for CBW defense in military combat. The issue of IND use arose in the Gulf War in the case of pyridostigmine bromide (PB), which was regarded as the most effective pretreatment against exposure to the nerve gas Soman, and pentavalent botulinum toxoid (BT)... 

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). 

Pulmonary Dyspnea CNS Cranial nerve deficits are universal Descending symmetric paralysis Gastrointestinal Constipation (later in course) OTHER FORMS OF BOTULISM ISOLATION/DECON PRECAUTIONS Droplet precautions Extensive precautions for laboratory personnel VACCINE Botulinum toxoid vaccine available but restricted in use to military and laboratory personnel. POSTEXPOSURE PROPHYLAXIS None... 

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). 

Fujihashi, K., Staats, H.F., Kozaki, S., and Pascual, D.W. 2007. Mucosal vaccine development for botulinum intoxication. Expert Rev. Vaccines 6 34 4,5. 

F. Vaccination. Vaccination is the preferred method of biological defense. Fully licensed vaccines are currently available for anthrax, cholera, plague and smallpox. Vaccines for botulinum toxoid, Q fever, Rift Valley fever, tularemia, and VEE currently exist as IND products and would be available only under protocol with informed consent, therefore would not be readily available on the battlefield. No vaccine is currently available either FDA licensed or under IND status, for glanders, brucellosis, Staphylococcus enterotoxin B, ricin, or T-2 mycotoxins. 

For reasons that are not completely understood, wounds are much more likely to be contaminated by Clostridium tetani than with Clostridium botulinum. Although an aggressive vaccination program has nearly eliminated tetanus in developed nations, the absence of universal tetanus vaccination in many third world countries results in over 300,000 cases annually. A large number of these occur in neonates, often by infection of the umbilical stump. ... 

The vaccine currently available is a toxoid that protects from serotypes A through E. This material is used under Investigational New Drug (IND) status, with a license held by the Centers for Disease Control and Prevention (CDC), Atlanta, Georgia. The toxoid was developed by scientists at Fort Detrick, Frederick, Maryland, during the 1950s.3 It is a formalin-fixed crude culture supernatant from strains of C botulinum that produce the appropriate serotypes. Vaccinations are administered at 0, 2, and 12 weeks, followed by annual booster doses. 

Vaccines. Anthrax and smallpox vaccines can be used before exposure and also for postexposuie prophylaxis. A pentavalent (ABODE) botulinum toxoid is currently used for laboratory workers at high risk of exposure. It is not effective for postexposure prophylaxis. Vaccines are not currently available for plague, tularemia, or viral hemorrhagic fevers. 

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