Human Monoclonal Antibodies that Bind Botulinum Toxins

结合肉毒杆菌毒素的人单克隆抗体

基本信息

批准号：
7341646
负责人：
SCOTT Kendall DESSAIN
金额：
$ 37.51万
依托单位：
LANKENAU INSTITUTE FOR MEDICAL RESEARCH
依托单位国家：
美国
项目类别：
财政年份：
2006
资助国家：
美国
起止时间：
2006-02-15 至 2011-01-31
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/7341646
关键词：
Amino Acid Sequence Antibodies Antibody Formation B-Lymphocytes Binding Biological Assay Bontoxilysin Botulinum Toxin Type A Botulinum Toxins Categories Cell Line Cloning Complex Development Epitopes Gene Family General Population Heparin Human Human Cloning Hybridomas In Vitro Individual Interleukin-6 Methods Military Personnel Monoclonal Antibodies Mus Names National Institute of Allergy and Infectious Disease Neuromuscular Blocking Agents Peripheral Blood Lymphocyte Platelet Factor 4 Polysaccharides Process Protocols documentation Publishing Purpose Research Personnel Screening procedure Seminal Serotyping Somatic Mutation Sorting - Cell Movement Source State Government Streptococcus pneumoniae Telomerase Testing Therapeutic Therapeutic antibodies Toxin Toxoids United States Vaccinated Vaccination Vaccines Vaccinia virus Viral Antigens Work base botulinum botulinum toxin type B chimeric antibody human monoclonal antibodies in vivo neutralizing antibody novel novel therapeutics programs research study response volunteer

项目摘要

DESCRIPTION (provided by applicant): Botulinum neurotoxin (BoNT) is an extremely potent neuromuscular blocker that has been designated a category A select bioterror agent by the United States Government because of its extreme lethality and its availability from environmental sources. Current countermeasures for BoNT exposure are insufficient, and there is an urgent need for therapeutic antibodies able to counteract the effects of BoNT exposure. Our working hypothesis is that a combination of human antibodies that bind BoNT will potently protect individuals from the complications of BoNT exposure. We have recently developed a novel hybridoma protocol for the cloning of human antibodies and have used it to clone antibodies that bind BoNT serotypes A and B. One of the serotype A antibodies is neutralizing in vivo. We plan to use our method to clone native human antibodies that bind and neutralize botulinum toxin serotypes A and B. For this purpose we will obtain peripheral blood lymphocytes from individuals vaccinated with the botulinum toxoid vaccine. We will assess in vitro and in vivo neutralizing activities of the cloned antibodies, singly and in combination. We will characterize the binding and primary sequences of the antibodies to determine the features that correlate with the ability to neutralize toxin and to cooperate synergistically in toxin neutralization. The primary result of these experiments will be the creation of combinations of cloned human antibodies that can effectively counteract BoNT/A and BoNT/B exposure.

描述（由申请人提供）：肉毒杆菌神经毒素（BONT）是一种极有效的神经肌肉阻滞剂，由于其极端的致死性及其可从环境来源的可用性而被美国政府指定为ASSECT的生物疗法。当前的BONT暴露对策不足，并且迫切需要能够抵消BONT暴露作用的治疗抗体。我们的工作假设是，结合BONT的人类抗体的结合将有力保护个体免受BONT暴露并发症的影响。我们最近开发了一种用于克隆人抗体的新型杂交瘤方案，并将其用于连接BONT血清型A和B的克隆抗体。一种血清型A抗体在体内中和。我们计划使用我们的方法来克隆结合和中和肉毒杆菌毒素血清型A和B的本地人类抗体。为此，我们将获得来自肉毒杆菌毒素疫苗接种的个体的外周血血液淋巴细胞。我们将单独和组合评估克隆抗体的体外和体内中和活性。我们将表征抗体的结合和主要序列，以确定与中和毒素中和毒素中和毒素中和的能力相关的特征。这些实验的主要结果将是创建可以有效抵消BONT/A和BONT/B/B暴露的克隆人类抗体的组合。