Transcutaneous Immunization (TCI) is a novel, painless, and noninvasive (skin patch) method of vaccination. TCI is being developed to improve the efficacy and safety of new and existing vaccines, eliminate the requirement for cold storage, reduce cost, and increase worldwide availability of vaccines. TCI takes advantage of the abundance and accessibility of a potent type of antigen presenting cell (APC), called Langerhans cells (LC), located throughout the superficial layer of the skin, the epidermis. The success of TCI depends on the use of immunostimulating adjuvants that activate LC to migrate to the draining lymph node and present antigen, initiating a specific immune response. Heat-labile enterotoxin (LT) from enterotoxigenic E. coli binds with a high affinity GM-1 receptor, which initiates the activation of LC to express co-stimulatory antigens and cytokines, MHC class II, and to take-up and process co-administered antigens. LT-mediated activation of LC culminates in antigen-specific systemic and mucosal immunity. Using TCI with LT as an adjuvant, Iomai has demonstrated in clinical trials that this is a safe and efficient method of vaccination for a wide range of vaccines, including inactivated viral vaccines, killed bacteria and multivalent high molecular weight (>800,000 Daltons) subunit vaccines. This phase I SBIR will establish the feasibility of topical vaccination with recombinant Protective Antigen from Bacillus anthracis, which is the principal component of existing anthrax vaccines and the lead candidate for a second-generation parenteral vaccine. Preclinical studies will define the amount of rPA antigen and LT adjuvant to elicit optimal systemic and mucosal immunity; compare the magnitude of the immune responses to full- and half-doses of the vaccine; complete toxicity studies to support phase I clinical trials; and complete a phase I clinical trial to assess the safety and immunogenicity of the rPA vaccine delivered by TCI. These studies will support expanded phase II efficacy and dose-optimization clinical trials that will be required to assess final patch formulation and the potential for pivotal studies for licensure.
