An improved targeted vaccine strategy against anthrax

NERCE项目9：针对炭疽病的改进的靶向疫苗策略--Ronald K.Taylor， 博士学位。 这项提议的目标是启动一种新的、有针对性的疫苗技术的开发。 与生物恐怖主义有关的病原体和那些对新出现的传染病负责的病原体。 针对特定抗原的疫苗可激发出极其迅速和有效的免疫反应。 专业抗原提呈细胞(APC)。除了诱导快速和强大的免疫反应外， 靶向疫苗可能更安全，更容易管理，并且需要非常低的剂量，从而减少 成本。 这个项目是基于学术研究人员和产业界之间的合作。抗原将会是 使用针对树突状细胞(DC)和其他APC的单抗 内吞受体、DEC-205和甘露糖受体(MR)。这些抗体被迅速内化，并 进入抗原呈递途径。以这种方式递送的抗原可诱导产生有效的抗体和 细胞毒性T淋巴细胞反应。重组抗原将在化学上和/或在基因上交联化 用已有的人源抗DEC-205和抗MR基因融合载体与mAb融合。 在过去的一年里，我们将炭疽重组保护性抗原(Rpa)与抗DEC-205融合，并进行了检测。 融合蛋白在小鼠体内诱导体液免疫反应的能力。我们正在着手实施同样的措施 利用弧菌重组TCPA研制霍乱靶向疫苗的策略 霍乱弧菌。

NERCE PROJECT 9: An improved targeted vaccine strategy against anthrax -Ronald K. Taylor, Ph.D. The goal of this proposal is to initiate the development of a novel, targeted vaccine technology against pathogens associated with bioterrorism and those that are responsible for emerging infectious diseases. Extremely rapid and potent immune responses are elicited by vaccines that target antigens specifically to professional antigen-presenting cells (APCs). In addition to inducing rapid and robust immune responses, targeted vaccines are potentially safer, easily administered, and require very low doses that leads to reduced cost. This project is based on a partnership between academic investigators and industry. Antigens will be targeted to dendritic cells (DCs) and other APCs using a monoclonal antibody (mAb) specific to the endocytic receptors, DEC-205 and mannose receptor (MR). These antibodies are rapidly internalized and gain access to the antigen presenting pathways. Antigens delivered in this way elicit potent antibody and cytotoxic T lymphocyte responses. Recombinant antigens will be chemically crosslinked and/or genetically fused to the mAbs using available human anti-DEC-205 and anti-MR gene fusion vectors. In the past year, we have fused recombinant protective antigen (rPA) of anthrax to anti-DEC-205 and tested the ability of the fusion to elicit humoral immune responses in mice. We are proceeding to apply the same strategy using anti-MR to develop a targeted vaccine for cholera, using recombinant TcpA from Vibrio cholerae.