Botulinum toxin is one of the six categories of pathogens that have been designated as Category A Select Agents by the Centers for Disease Control. The toxin, which is generally acknowledged to be the most potent biological poison known, enters the body and acts on peripheral cholinergic nerve endings to cause paralysis of transmission. In seriously poisoned patients, this can include paralysis of the muscles of respiration, which can lead to death. A Presidential Blue Ribbon Panel has urged that medical countermeasures against the toxin be developed, including a vaccine against the toxin. There are 8 known serotypes of toxin (A to H), but only three of these account for almost all human illnesses (A, B, and E). Therefore, the Blue Ribbon Panel has proposed that highest priority be assigned to a trivalent A/B/E vaccine. Unfortunately, since the publication of the Panel's recommendations, there is not a single trivalent vaccine that has obtained regulatory approval. In fact, there is not a single trivalent vaccine candidate that is in clinical trials. There is a vccine candidate composed of recombinant antigens that began as a trivalent formulation, but the E antigen has subsequently been deleted leaving only an A/B divalent vaccine. These recombinant polypeptides are formulated as an injection vaccine rather than a more preferable needle-free formulation (i.e., mucosal or transdermal), and the antigens retain the ability to bind to nerve endings and therefore have the potential to evoke adverse neurologic side effects. In view of these serious shortcomings, the applicant and her colleagues at Inventox will combine proprietary technology and a series of discoveries about sites and mechanisms of antibody action to create a trivalent A/B/E vaccine that: a.) meets the mandate of the Blue Ribbon Panel, b.) can be administered by a mucosal route (i.e., needle-free vaccine), c.) does not have the potential to evoke adverse neurologic effects, d.) can evoke both a secretory IgA response and a circulating IgG response, and e.) can produce three levels of protection against poisoning. These three levels of protection include IgA-mediated blockade of toxin absorption into the body, IgG-mediated enhancement of toxin clearance from the general circulation, and IgG-mediated blockade of toxin binding to target cholinergic nerve endings. Overall, this vaccine will be superior to any other product described, and will be a substantial advancement over the current state of the art. In addition, the techniques that are used to create the high priority trivalent vaccine can ultimately serve as a model for developing vaccine candidates against the remaining five serotypes.
Botulinum toxin is an extraordinarily potent substance that has the potential to be used as an agent of bioterrorism. A Presidential Blue Ribbon Panel has urged that a trivalent vaccine be developed that will protect against the three serotypes of botulinum toxin that are most often implicated in human illness. The applicant and her colleagues will utilize novel patent technology, plus a series of new discoveries, to create a trivalent vaccine that is needle-free, and that is also free of potential to evoke certain kinds of adverse effects.