Human immunotherapeutics for Biodefense Applications

被动免疫疗法是一种非常有效的治疗感染性疾病的方法，无论它们是自然获得的还是生物战的结果。在转基因动物中大量开发和生产的人多克隆抗体将为生物战剂的爆发提供即时治疗。Origen Therapeutics正在开发转基因鸡，这种鸡将产生抗原特异性的体液免疫反应，由高亲和力和生物防御应用特异性的全人多克隆抗体组成。与哺乳动物相比，鸡在抗体产生方面的主要优势是母鸡将大量母源抗体存款在蛋黄中，蛋黄是一种无菌且方便的包装，并且鸡通常在SPF设施中生长。在所提出的工作中，已知特异性的人表面IgM抗体将在体内鸡B淋巴细胞中表达。该实验将解决人IgM驱动鸡中抗体应答所需的基本细胞过程的能力，即B细胞发育、法氏囊中的增殖和向外周的迁移。这项工作将证明鸡免疫系统可以在其B淋巴细胞中产生人抗体，并且人抗体可以在鸡B细胞和下游生物防御应用中正常发挥作用。

DESCRIPTION (provided by applicant): Passive immunotherapy is a highly effective treatment for infectious diseases, whether they are acquired naturally or as a result of biological warfare. Human polyclonal antibodies developed and produced in quantity in transgenic animals will provide an immediate therapy to an outbreak of a biological warfare agent. Origen Therapeutics is developing transgenic chickens that will raise an antigen-specific, humoral immune response consisting of fully human polyclonal antibodies of high avidity and specificity for biodefense applications. The chief advantages of chickens over mammals for antibody production are that hens deposit large amounts of maternal antibodies in the egg yolk, a sterile and convenient package, and that chickens are routinely grown in SPF facilities. In the proposed work, a human surface IgM antibody of known specificity will be expressed in chicken B-lymphocytes in vivo. The experiments will address the ability of human IgM to drive the fundamental cellular processes required for antibody responses in the chicken, namely B cell development, proliferation in the bursa of Fabricius and migration to the periphery. This work will be proof of principle that the chicken immune system can produce human antibodies in its B-lymphocytes and that human antibody can function properly both in the context of the chicken B cell and in downstream biodefense applications.