Research Project
6834873
DESCRIPTION (provided by applicant): Anthrax, an infectious disease caused by Bacillus anthracis, became a pressing concern because of its potential biowarfare use, most likely via aerosolized anthrax spore dissemination, resulting in deadly inhalation anthrax. The current vaccine, which confers protection by inducing antibodies against anthrax toxin subunit Protective Antigen (PA), has significant drawbacks including manufacturing issues, lack of standardization and quality control, the need for repeated injections, and frequent occurrence of side effects, making it inadequate for use in large populations. A new vaccine is urgently needed. A DNA vaccine directed against anthrax toxin would be economical, relatively easy to prepare, store and standardize, should induce few, if any, side effects. The method of application of a DNA vaccine is critical for efficacy. Vaccine will be delivered by electroporation because this method provides consistent, high level, scalable immunogen expression, which correlates with high magnitude, durable antibody responses. Ichor has already developed a vaccine applicator suitable for clinical studies. Under SBIR Phase I feasibility studies, Ichor has demonstrated, using a research plasmid, that electroporation-based immunization against-PA, induced robust anti-PA antibody response and long term immunological memory after three or fewer immunizations in small rodents. The procedure was dose efficient, scalable to larger species and induced the formation of protective antibodies. Following completion of the Phase I objectives, Ichor has started designing vaccine candidates and is in the process of validating them in mouse immunological studies. Under SBIR Phase II, Ichor's goal is to develop an effective, simple and reliable anthrax vaccine that provide long-term protection after a minimum number of immunizations. Under Specific Aim #1, exploratory toxicological studies will be conducted in mice to eliminate construct candidates with unacceptable toxic side effects. Two or three selected constructs will then be tested in immunological studies in rabbits. Based on the results, one single construct will be selected and tested in GLP efficacy studies in rabbits. These studies will assess protection of vaccinated rabbits against inhalation challenge with live B. anthracis spores. If adequate protection is provided by the vaccine candidate, studies will progress into Year 2. Under Specific Aim #2, formal GLP immunization studies will be conducted in rhesus monkeys with immunological, safety and efficacy endpoints. This will help select a proposed human dose. Based on that dose, formal safety studies will be conducted in Specific Aim #3. These will include biodistribution and integration studies in rats and a toxicological evaluation in rabbits. Following the completion of the studies, Ichor will initiate pre- IND discussions with the FDA.
