Mucous membranes are the primary routes of entry for a variety of disease carrying agents, including anthrax. Many human pathogens enter and replicate at the mucosal surface before causing systemic infection. It is particularly important to curtail infection at the mucosal surface before persistent infection of systemic sites initiated. Oral immunization has been shown to result in the induction of secretory, as well as systemic, immune responses. The overall goal of the proposed program is to develop an oral vaccine delivery system that is both capable of protecting anthrax plasmid immunogens in the stomach and of providing optimized plasmid release in the colon by bioadherence. In the Phase I program, the plasmid immunogens are DNA plasmids encoding the recombinant protective antigen (PA) and the lethal factor (LF) of anthrax. The early part of the Phase I workscope will address the formulation of PA/LF delivery system comprised of primary and secondary carriers and to evaluate the bioadhesive and release properties of the dose form. The formulation that demonstrates bioadhesion and multiphasic release in the in vitro models will then be used in Phase I to determine antibody responses correlative to protective efficacy in mice. The Phase I feasibility will be defined by the capacity of the formulation to elicit antibody responses at a level sufficient to suggest protective efficacy against anthrax spore challenge.
