DNA Plasmid Mucosally Enhanced Anthrax Delivery Vaccine

描述（由申请人提供）：粘膜是各种疾病携带剂（包括炭疽）的主要进入途径。 许多人类病原体在引起全身感染之前进入粘膜表面并在粘膜表面复制。 特别重要的是，在全身部位开始持续感染之前，减少粘膜表面的感染。 口服免疫已显示导致诱导分泌性以及全身性免疫应答。 拟议计划的总体目标是开发一种口服疫苗递送系统，该系统既能够保护胃中的炭疽质粒免疫原，又能够通过生物粘附在结肠中提供优化的质粒释放。 在I期计划中，质粒免疫原是编码炭疽的重组保护性抗原（PA）和致死因子（LF）的DNA质粒。 I期工作范围的早期部分将讨论由一级和二级载体组成的PA/LF给药系统的配方，并评价剂型的生物粘附性和释放特性。 在体外模型中证明生物粘附和多相释放的制剂随后将用于I期，以确定与小鼠保护效力相关的抗体应答。I期可行性将通过制剂在足以表明对炭疽孢子挑战的保护效力的水平上引发抗体应答的能力来定义。

DESCRIPTION (provided by applicant): 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.