Highly Stable, Anthrax-specific Shark Antibody Fragment

高度稳定的炭疽特异性鲨鱼抗体片段

• 批准号: 6675141
• 负责人: Martin F Flajnik
• 金额: $ 27.53万
• 依托单位: UNIVERSITY OF MARYLAND BALTIMORE
• 依托单位国家: 美国
• 财政年份: 2003
• 资助国家: 美国
• 起止时间: 2003-07-15 至 2005-06-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6675141
• 关键词: Bacillus anthracis; active immunization; anthrax; antibody; antibody formation; antibody receptor; antibody specificity; antigen receptors; binding sites; biohazard detection; biological products; biotechnology; bioterrorism /chemical warfare; biotherapeutic agent; diagnosis design /evaluation; drug design /synthesis /production; drug discovery /isolation; enzyme linked immunosorbent assay; gene mutation; genetic library; immunoglobulin isotypes; molecular cloning; polymerase chain reaction; receptor binding; sharks; vector vaccine

DESCRIPTION (provided by applicant): There is an urgent demand for the development of innovative diagnostic and therapeutic products for widespread use in the bio-defense field, especially against Category A pathogens such as Bacillus anthracis. To this end it is desirable that the developed products show high specificity for their target and high stability to denaturation. Recent work identified a novel antibody isotype, called IgNAR (novel antigen receptor) in the serum of nurse sharks. This molecule is unusual as the variable (V) regions, responsible for binding antigen, did not form a dimer as in conventional antibodies but are able to bind antigen as individual soluble domains. Due to its high level of targeted somatic hypermutation IgNAR appears to be the molecule responsible for the true adaptive immune system in cartilaginous fish. The aim of this project is to isolate specific and highly stable single domain antibody fragments from nurse sharks immunized with the recombinant form of protective antigen (rPA) from B. anthracis. Due to the unique nature of these molecules, if this initial antigen proves successful, we envisage this technique will provide a platform technology which could easily be utilized to supply similar fragments for use as diagnostic or therapeutic tools for limitless other targets of interest for bio-defense.

描述(申请人提供)：迫切需要开发创新的诊断和治疗产品，广泛用于生物防御领域，特别是针对A类病原体，如炭疽杆菌。为此，所开发的产物表现出高度的靶向性和高度的变性稳定性是可取的。最近的工作在护士鲨的血清中发现了一种新的抗体亚型，称为IgNAR(新抗原受体)。这种分子是不寻常的，因为负责结合抗原的可变区(V)不像传统抗体那样形成二聚体，但能够以单个可溶域的形式结合抗原。由于其高水平的靶向体细胞超突变，IgNAR似乎是软骨鱼类真正适应性免疫系统的负责分子。本项目的目的是从用炭疽杆菌重组保护性抗原(RPA)免疫的护士鲨中分离出特异性和高度稳定的单域抗体片段。由于这些分子的独特性质，如果这种初始抗原被证明是成功的，我们预计这项技术将提供一种平台技术，可以很容易地提供类似的片段，用作诊断或治疗工具，用于无限的其他感兴趣的生物防御目标。