? Botulinum neurotoxin, an NIAID class A agent, has been weaponized, thus dictating an urgent need for a safe, efficacious vaccine that will protect against all seven known serotypes of the toxin. The two specific aims of this project are first, the fast-track development (within one-to-two years) of a safe and efficacious pentavalent vaccine for the neurotoxin that will provide immunologic protection against toxin serotypes A, B, C, E and F; and second, development of a fully protective heptavalent vaccine to include serotypes D and G within five years. The partners for this project include representatives from industry (DynPort Vaccine Company LLC:DVC), academe (University of Nebraska-Lincoln: UNL and the University of Colorado Health Sciences Center: UC-HSC) and the military (U.S. Army Medical Research Institute of Infectious Diseases: USAMRIID). The approach we will take to achieve these aims is based upon the successful development and expression in the yeast, P. pastoris, of serotype-specific toxin heavy-chain protein fragments, that, when purified and administered to experimental animals, provide protective immunity against challenge with lethal doses of the botulinum neurotoxins. Monovalent vaccine candidates against serotypes A and B are already in current Good Manufacturing Practices pilot production, and vaccine candidates for serotypes C, E and F are in advanced stages of process development at UNL, thus facilitating the likelihood of success of the first specific aim. The methodologies established for development of vaccine candidates against serotypes A, B, C, E and F provide a rich body of knowledge on which the development of equivalent vaccine candidates for the remaining two serotypes (D and G) will be based, thus facilitating accomplishment of the second specific aim. UC-HSC will contribute expertise in formulating and stabilizing both liquid and lyophilized vaccines, essential for the achievement of both specific aims. The proposed research will have a high probability of success, in part, because of the highly innovative approach of having the industry partner, DVC, whose business model is vaccine development through management and coordination of scientific subcontractors, serve as the lead institution. The impact of the successful completion of the project will be an effective heptavalent vaccine for prophylactic immune defense against botulinum neurotoxin within an expedited, but realistic, timeframe and elimination of botulinum toxin as a weapon of mass destruction. ? ?
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