An improved targeted vaccine strategy against anthrax

改进的针对炭疽的靶向疫苗策略

• 批准号: 7645359
• 负责人: RONALD K TAYLOR
• 金额: $ 25.54万
• 依托单位: HARVARD MEDICAL SCHOOL
• 依托单位国家: 美国
• 财政年份: 2008
• 资助国家: 美国
• 起止时间: 2008-03-01 至 2009-02-28
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7645359
• 关键词: Animal Model; Anthrax disease; Antibodies; Antigen Targeting; Antigen-Presenting Cells; Antigens; Bioterrorism; Cholera; Cholera Vaccine; Cytotoxic T-Lymphocytes; DEC-205 receptor; Dendritic Cells; Development; Doctor of Philosophy; Dose; Emerging Communicable Diseases; Enzyme-Linked Immunosorbent Assay; Evaluation; Gene Fusion; Genetic; Goals; Human; Immune response; Immunology; Immunotherapy; Industry; Lead; Length; Microbiology; Monitor; Monoclonal Antibodies; Mus; Organism; Pathway interactions; Plasmid Cloning Vector; Receptor Gene; Recombinants; Research Personnel; Scheme; System; Technology; Testing; Therapeutic; Toxin; Transgenic Mice; Universities; Vaccines; Vibrio cholerae; Western Blotting; Work; Yeasts; anthrax protective factor; base; cost; crosslink; experience; hybrid protein; improved; mannose receptor; medical schools; nonhuman primate; novel; pathogen; protein purification; response; size; vaccine efficacy; vaccine-induced immunity; vector

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.

NERCE项目9：一种针对炭疽的改进的靶向疫苗策略-罗纳德K。泰勒先生， 博士 该提案的目标是启动一种新的靶向疫苗技术的开发， 与生物恐怖主义有关的病原体和造成新出现的传染病的病原体。 通过特异性靶向抗原的疫苗引发极其快速和有效的免疫应答， 专业抗原递呈细胞（APC）。除了诱导快速和强有力的免疫应答外， 靶向疫苗可能更安全，易于管理，并且需要非常低的剂量，从而减少 成本 该项目是基于学术研究人员和行业之间的伙伴关系。抗原将是 使用对树突状细胞（DC）和其它APC特异的单克隆抗体（mAb）靶向DC和其它APC。 胞吞受体DEC-205和甘露糖受体（MR）。这些抗体被迅速内化， 进入抗原呈递途径。以这种方式递送的抗原引发有效的抗体， 细胞毒性T淋巴细胞反应。重组抗原将被化学交联和/或遗传交联。 使用可获得的人抗DEC-205和抗MR基因融合载体与mAb融合。 在过去的一年里，我们将炭疽的重组保护性抗原（rPA）融合到抗DEC-205上， 融合体在小鼠中引发体液免疫应答的能力。我们正着手实施同样的 利用重组弧菌TcpA研制霍乱靶向疫苗的策略 胆汁。