Due to its ease of production and transport, Botulinum neurotoxin (BoNT), the most potent toxin known, is a likely agent of choice for biowarfare. Polyclonal antibodies are the best option to neutralize BoNT since their multivalency facilitates their ability to bind and neutralize toxins of various serotypes in vivo. Antiserum produced in horses and distributed by the CDC is an effective therapeutic, but it is also immunogenic and therefore, the case of serum sickness and anaphylaxis. Clearly the ready availability of a potent human antibody preparation would be a great improvement for the management of botulinum intoxication. To produce a safe, potent and non-immunogenic botulinum antiserum our partner, Therapeutic Human Polyclonals (THP), has humanized a new class of antibodies, polyclonals, using a novel genetic engineering approach. They have generated founder transgenic rabbits that express humanized immunoglobulin light or heavy chains. These founders have been crossbred to produce double transgenic offspring that express human immunoglobulins, both light and heavy chains. We will utilize these rabbits to develop and produce a polyclonal antiserum pharmaceutical against BoNT in preparation for testing in human clinical trials. For this purpose a series of tasks will be performed and completed including optimizing vaccination procedures and immunogens for the rabbits, developing a plasmaphoresis machine for rabbits to increase the productivity of the process more than four-fold, producing a GMP lot of the polyclonal antibody preparation, (ToxBIock), conducting preclinical safety and immunogenicity studies with ToxBIock and filing an IND.
| Held, Daniel M; Shurtleff, Amy C; Fields, Scott et al. (2010) Vaccination of rabbits with an alkylated toxoid rapidly elicits potent neutralizing antibodies against botulinum neurotoxin serotype B. Clin Vaccine Immunol 17:930-6 |
