Botulism is a severe neuroparalytic disease caused by toxins produced by several 
Clostridium species. Botulinum toxin has been of concern to the US military and 
its allies as a biowarfare weapon since World War II and, in more recent times, 
by the Centers for Disease Control and Prevention (CDC) as a potential 
bioterrorist threat to the public. The most effective means of defending against 
the toxin is by inducing a protective immune response through vaccination. 
Vaccination with an appropriate antigen will produce neutralizing antibodies 
that will bind to and clear toxin from the circulation before it can enter nerve 
cells and block neurotransmission. Immunity from botulism, however, has the 
disadvantage of precluding an individual from realizing the potential benefits 
of therapeutic botulinum toxin, if such a need were to arise. Botulinum toxin 
has been used in the treatment of numerous neuromuscular, autonomic, and sensory 
disorders since it was first approved for the management of strabismus and 
blepharospasm by the Food and Drug Administration (FDA) in 1989. Notwithstanding 
the value of the neurotoxin as a therapeutic drug, vaccines have been and will 
continue to be an important line of defense for those who work with the toxin 
(at-risk workers) and a select population of the military, law enforcement, and 
first responders. The first vaccine used to protect against botulinum neurotoxin 
was a chemically detoxified extract from Clostridium botulinum. A Pentavalent 
botulinum toxoid (PBT) vaccine in service today is administered under an 
Investigational New Drug (IND) application held by the CDC. Recombinant subunit 
vaccines are in development and a bivalent H(c) vaccine (rBV A/B (Pichia 
pastoris)) is presently being evaluated in a phase II clinical trial. This 
review focuses on botulism and the development of vaccines for its prevention.