Toward Ideal Vaccines for Emerging Infectious Diseases Research

新的感染源的不断出现和对故意部署病原体的担忧已经 强调了疫苗发现、生产和管理方面对新技术的需求。众多人 重组DNA方法的优势使基于基因的疫苗成为一种有吸引力的方式。到目前为止 缺点是它们的免疫原性普遍较低。在某些情况下，一种或多种佐剂 已经能够提高反应水平；然而，每个抗原和佐剂组合必须是 经验性地确定。我们的研究旨在开发一种单一平台的方法来传递任何基因 将提高免疫效力和扩大粘膜反应性的疫苗，不需要定制佐剂。 这种方法是基于纳米颗粒的高免疫原性和遗传方式的灵活性。 我们正在测试一种基因方法，以简单地构建并灵活地传递高免疫原性抗原 呈现在纳米颗粒的表面。这些将被设计为通过以下任一方式有效地交付 全身或粘膜途径。炭疽杆菌PA、流感HA以及牛痘B5R和A33R抗原将是 用作模特。基因传递的粒子格式将以基因和经典为基准 蛋白质亚单位疫苗。一旦确定了免疫刺激特征，它们的效用就是强大的 分子疫苗将在疾病的动物模型中进行评估。如果成功，该项目将提供 朝向快速设计、生产和管理安全和广泛有效的目标的关键 针对新出现、再次出现和生物治疗疾病的疫苗。

Continued emergence of new infectious agents and concerns for intentional pathogen deployment has highlighted needs for new technologies in vaccine discovery, production and administration. The many advantages of recombinant-DNA methods make gene-based vaccines an attractive modality. To date the drawback has been their generally low immunogenicity. In some cases one or more of a variety of adjuvants have been able to enhance response levels; however, each antigen and adjuvant combination must be empirically identified. Our studies are aimed at developing a single-platform approach for delivering any gene vaccine that will raise immune potency and broaden mucosal responsiveness, without customized adjuvant. This approach is based on the high immunogenicity of nanoparticles, and the flexibility of a genetic modality. We are testing a genetic approach to simply build and flexibly deliver highly immunogenic antigens presented on the surface of nanoparticles. These will be designed to be effectively delivered via either systemic or mucosal routes. The anthrax PA, influenza HA, and vaccinia B5R and A33R antigens will be used as models. The genetically delivered particle formats will be benchmarked to gene and classical protein subunit vaccines. Once immune stimulation profiles have been determined their utility as robust molecular vaccines will be evaluated in animal models of disease. If successful this project will provide the ynchpin toward the goal of rapidly designing, producing, and administering safe and broadly efficacious vaccines to both emerging, re-emerging and biothreat diseases.