Highly Stable, Anthrax-specific Shark Antibody Fragment

描述（由申请人提供）：迫切需要开发创新的诊断和治疗产品，以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，希望开发的产品显示出对其靶标的高特异性和对变性的高稳定性。最近的工作在护士鲨的血清中发现了一种新的抗体同种型，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（V）区不像常规抗体那样形成二聚体，而是能够作为单独的可溶性结构域结合抗原。由于其高水平的靶向体细胞超突变，IgNAR似乎是负责软骨鱼中真正适应性免疫系统的分子。本项目的目的是从用来自B的重组形式的保护性抗原（rPA）免疫的护士鲨中分离特异性和高度稳定的单域抗体片段。炭疽病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，我们设想这种技术将提供一种平台技术，该技术可以很容易地用于提供类似的片段，用作生物防御的无限其他感兴趣的靶标的诊断或治疗工具。

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.