DNA Plasmid Mucosally Enhanced Anthrax Delivery Vaccine

描述（由申请人提供）：粘膜是包括炭疽在内的各种疾病携带因子的主要进入途径。许多人类病原体在引起全身感染之前进入并在粘膜表面复制。在系统性部位持续感染开始之前，减少粘膜表面感染尤为重要。口服免疫已被证明可以诱导分泌性和全身免疫反应。拟议项目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提供优化的质粒在结肠中的释放。在I期项目中，质粒免疫原是编码重组保护抗原（PA）和炭疽致死因子（LF）的DNA质粒。第一阶段工作范围的早期部分将涉及由一级和二级载体组成的PA/LF递送系统的制定，并评估剂型的生物粘附和释放特性。在体外模型中表现出生物黏附和多相释放的配方将用于第一阶段，以确定与小鼠保护功效相关的抗体反应。第一阶段的可行性将由制剂的能力来确定，以引起抗体反应的水平足以表明对炭疽孢子攻击的保护功效。

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.