Botulism is a neuromuscular poisoning caused by clostridial neurotoxins. Humans are exposed to neurotoxins produced by Clostridial botulinum through food poisoning. Incidences of wound botulism and a colonizing infection of neonates known as infant botulism are rare. Although the infective microorganism can be treated by antibiotics, there exists no specific drug therapy for botulinum toxins. Toxoids, as in formalin-inactivated vaccines, can be prepared for active immunization of individuals who are likely to be exposed to C. Botulinum or its toxins. However, problems associated with such immunization, including the need for more than a single dose of expensive, multivalent toxoids, and concerns about reversion of the toxoids to toxins created a need for single-dose immunization with a safe vaccine. Recent availability of recombinant fragment C botulinum (r-FCBt) vaccine and absorbable gel-forming carriers justified pursuing the proposed program. The objective of Phase I is to determine the feasibility of using absorbable gel-forming and micro-spherical polyester carriers in developing a r-FCBt vaccine for intranasal and subcutaneous immunization. Phase I entails (1) preparing and characterizing the polymeric carriers; (2) formulating and evaluating, in mice, candidate controlled release systems using Type E and F r-FCBt vaccines; (3) determining the antibody response; and (4) conducting challenge studies with individual homologous serotypes. Phase I results will be used to design Phase II plans that include (1) studying immunization and protection of all r-FCBt vaccines (A, B, C, D, E, F, and G) against highest dose of homologous and possibly heterologous toxin serotypes; (2) developing, scaling-up, and evaluating a multivalent r-FCBt vaccine; and (3) conducting a brief safety study on the multivalent vaccine.
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