Therapeutic antibodies for lethal anthrax infection

致命炭疽感染的治疗性抗体

• 批准号: 6691548
• 负责人: JOHN E HERRMANN
• 金额: $ 26.31万
• 依托单位: ANTIBODY SCIENCE, INC.
• 依托单位国家: 美国
• 财政年份: 2003
• 资助国家: 美国
• 起止时间: 2003-08-01 至 2006-07-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6691548
• 关键词: Bacillus anthracis; anthrax; anthrax vaccines; bacterial antigens; bacterial toxins; drug screening /evaluation; immunoglobulin G; immunologic substance development /preparation; laboratory rabbit; neutralizing antibody; passive immunization; plasmids; sheep; vaccine development; vaccine evaluation

DESCRIPTION (provided by applicant): The overall objective of this phase I SBIR proposal is to develop therapeutic antibodies for passive immunotherapy in acute anthrax, including the highly lethal inhalational form of anthrax. We will use codon-optimized plasmid DNAs (DNA vaccines) to immunize experimental animals to produce anti-anthrax antibodies suitable for human use in passive immunization. This would enable an immunization strategy that would supplement antibiotic therapy regimens to improve the survival of patients with anthrax. The antibodies prepared will be high titer, specific polyclonal antibodies to Bacillus anthracis protective antigen (PA) that can neutralize PA and block formation of anthrax toxin complexes. As part of these studies we will purify IgG from hyperimmune serum and determine the levels of neutralizing activity obtained. Because of the high failure rate of antibiotic therapy there is a clear need for development of a strategy for passive immunization against anthrax. In our preliminary studies, we at Antibody Sciences, Inc. have obtained toxin-neutralizing antibody by DNA immunization equivalent to the protective titers obtained by others in animals that received active immunization with an anthrax vaccine. Our techniques for DNA immunization permit quick production of high titer antisera without the need for purification of B. anthracis antigens from bacterial cultures or from cell-culture expressed antigens. DNA immunization offers a highly standardized and low cost process to produce large quantity of antibodies. Therefore, the high titer antibody we can produce will enable stockpiling of sufficient quantities of antibody for immunotherapy should attacks with B. anthracis occur. At the end of this phase 1 study, a standardized schedule will be established in phase II to prepare for large-scale production and testing of this much needed, perhaps essential, product in biodefense against anthrax attacks.

描述（由申请人提供）：该阶段I SBIR提案的总体目标是开发用于急性炭疽病的被动免疫疗法的治疗抗体，包括高致命的吸入形式的炭疽形式。我们将使用密码子优化的质粒DNA（DNA疫苗）来免疫实验动物，以产生适合人类在被动免疫中使用的抗人类抗体。这将实现一种免疫策略，该策略将补充抗生素治疗方案，以改善炭疽患者的存活率。制备的抗体将是对炭疽芽孢杆菌保护抗原（PA）的高滴度，特异性的多克隆抗体，可以中和PA并阻断炭疽毒素复合物的形成。作为这些研究的一部分，我们将从高免疫血清纯化IgG，并确定所获得的中和活性的水平。 由于抗生素疗法的失败率很高，因此显然需要制定针对炭疽的被动免疫的策略。在我们的初步研究中，抗体科学，Inc。的我们通过DNA免疫获得了毒素中和抗体，等于其他动物在动物中获得的保护性滴度等于接受炭疽疫苗的主动免疫。我们的DNA免疫技术可以快速生产高滴度抗血清，而无需从细菌培养物或细胞培养表达的抗原中纯化炭疽芽孢杆菌抗原。 DNA免疫提供了高度标准化和低成本的过程，可产生大量抗体。因此，我们可以产生的高滴度抗体将使足够数量的免疫疗法库存库存，应发生炭疽芽孢杆菌的攻击。在这一第一阶段研究的结束时，将在第二阶段建立标准化的时间表，以准备大规模生产和测试这种急需的生物（也许是必不可少的产品），以针对炭疽攻击。