Vaccination plays a central role in a biodefense strategy and is the established intervention against anthrax. Further development of both existing and new biodefense vaccines is required to improve the anthrax vaccine acceptability and better tailor the means of delivery to make the utilization of the vaccine in mass immunization campaigns more feasible. Transcutaneous immunization is a new approach to needle-free and device-free immunization using a patch to deliver vaccine antigens and potent adjuvants. Topical skin immunization takes advantage of the immunobiology of the skin leading to safe and effective systemic immune responses. The use of the adjuvant LT has been shown to safely augment the immune response in the context of the skin in both preclinical and clinical settings. This phase II SBIR proposal will focus on the development of a dry self-adhesive anthrax vaccine patch, which can be manufactured (cGMP) and is practical to apply in the clinic. A dry, adhesive patch has been shown to effectively and safely deliver LT in clinical settings.
The specific aims of this proposal are to assess the biological activity and potency of LT when formulated with the anthrax vaccine in adhesive blends containing both LT and rPA; to characterize the in vitro release and recovery of rPA and LT from formulated dry patches; to screen antigen release, delivery and adjuvanticity by assessing the systemic immune responses elicited by LT/rPA adhesive patches; to test the functionality of antigen released form LT/rPA adhesive patches in rabbit challenge models; to assess the stability of rPA and LT in dry adhesive patch formulations; to develop a pilot scale (lot size >1,000 patches) manufacturing process for cGMP production of rPNLT patches that could support clinical trials. These activities will prepare the groundwork for clinical evaluation of an anthrax patch in a parallel clinical development program, funded outside of this Phase II SBIR. The development of a formulated, manufacturable dry adhesive patch anthrax vaccine that is simple to apply and has strong patient acceptance will significantly advance the transcutaneous immunization technology and lead to broadening of this promising approach to vaccination. ? ?
