Toward Ideal Vaccines for Emerging Infectious Diseases Research

新的传染性病原体的不断出现和对故意部署病原体的担忧， 强调了在疫苗发现、生产和管理方面对新技术的需求。的许多 重组DNA方法的优点使得基于基因的疫苗成为一种有吸引力的形式。迄今 缺点是它们的免疫原性通常较低。在一些情况下，多种佐剂中的一种或多种可用于治疗癌症。 已经能够增强应答水平;然而，每种抗原和佐剂组合必须 经验鉴定。我们的研究旨在开发一种单一平台的方法， 疫苗将提高免疫效力并扩大粘膜反应性，而无需定制佐剂。 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，可以简单地构建和灵活地提供高免疫原性抗原 呈现在纳米颗粒的表面上。这些将被设计为通过以下方式有效地提供： 全身或粘膜途径。炭疽PA、流感HA和牛痘B5 R和A33 R抗原将被 用作模型。基因递送的颗粒形式将以基因和经典为基准。 蛋白亚单位疫苗。一旦确定了免疫刺激特征， 将在疾病的动物模型中评估分子疫苗。如果成功，该项目将提供 朝着快速设计、生产和管理安全和广泛有效的目标迈进 新出现的、重新出现的和具有生物威胁的疾病的疫苗。

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.