Liposomal Adjuvant for Vaccine Development

描述（由申请人提供）：预防传染病爆发的基因工程疫苗的发展取得了进展，促使对针对一些病原体的疫苗接种策略进行了重新评估。我们一直在开发一种新的免疫模型，它基于一种灵活的抗原递送平台技术，可以对多种抗原提供高效的免疫反应。通常，靶抗原在基因上融合到疏水蛋白结构域，该结构域被设计成与脂质体膜相结合。所得抗原融合蛋白在适当条件下是水溶性的，允许使用商业上可行的制备程序分离和操作重组蛋白。我们之前已经证明，这种脂质体疫苗复合物在刺激啮齿动物对病毒和细菌病原体的主动保护性免疫反应方面非常有效。然而，有必要改进佐剂配方，以便方便地修改和用作疫苗研究的工具。为了满足这一需求，我们建议在SBIR I期申请中修改我们的疫苗技术，使靶抗原可以简单地化学偶联到脂质体表面，而不必产生重组融合蛋白。我们的中心假设是，可以制备一种高度免疫原性的脂质体制剂，它可以很容易地与靶抗原化学结合，然后用作疫苗。以炭疽的病原炭疽芽孢杆菌为模型致病菌，我们从炭疽中选择了两个关键的靶抗原，为我们提出的疫苗技术修改建立概念证明。在成功完成拟议的研究后，我们改良的脂质体疫苗平台技术将被开发出来，面向疫苗研究界进行一般销售。这将使疫苗研究人员有机会利用我们的抗原递送系统，通过一种试剂盒，人们只需在适当的交联剂存在下将靶抗原与脂质体混合，如果需要的话，纯化抗原偶联脂质体，然后将它们用作疫苗研究的研究工具。此外，还可能发现可开发成下一代炭疽疫苗的脂质体制剂。

DESCRIPTION (provided by applicant): Advances in the development of genetically engineered vaccines to prevent outbreaks of infectious disease have prompted a re-evaluation of vaccination strategies against a number of pathogens. We have been developing a new model of immunization that is based on a flexible antigen delivery platform technology that provides highly effective immune responses to a wide range of antigens. Typically, the target antigen is genetically fused to a hydrophobic protein domain that has been engineered to associate with liposomal membranes. The resulting antigen fusion protein is water soluble under the appropriate conditions, allowing for the isolation and manipulation of the recombinant protein using commercially viable preparative procedures. We have previously shown that this liposomal vaccine complex is highly effective at stimulating active protective immune responses in rodents against viral and bacterial pathogens. However, there is a need for improved adjuvant formulations that can be conveniently modified and used as a tool in vaccine research studies. To address this need, we propose in this SBIR Phase I application to modify our vaccine technology so that a target antigen can simply be chemically coupled to the surface of our liposome without having to produce the recombinant fusion protein. Our central hypothesis is that a highly immunogenic liposome formulation can be prepared that can be easily conjugated with a target antigen chemically and then used as a vaccine. Using Bacillus anthracis, the etiologic agent of anthrax, as a model disease causing pathogen, we have selected two critical target antigens from anthrax to establish the proof of concept for the proposed modification to our vaccine technology. Upon the successful completion of the proposed studies, our modified liposomal vaccine platform technology would then be developed for general sale to the vaccine research community. This would give vaccine researchers an opportunity to take advantage of our antigen delivery system through a kit in which one would simply mix the target antigen with the liposomes in the presence of the appropriate crosslinker, purify the antigen conjugated liposomes if desired, and then use them as a research tool in their vaccination studies. Moreover, liposomal formulations might also be discovered that could be developed into the next generation anthrax vaccine.