HUMAN MONOCLONAL ANTIBODIES TO CATEGORY A PATHOGENS

从历史上看，产生分泌人类永生化B细胞的IgG抗体是非常困难的 产生大量的抗体。这一直是人类B细胞研究的主要绊脚石 免疫学，以及对人类中和抗体的理解。此外，中和抗体 可能是有价值的治疗剂。最近已经证明，人类杂交瘤可以是 使用人类骨髓瘤细胞系Karpas 707H，使其分泌大量抗体。 使用这项新技术，我们建议从吸入性炭疽中分离出炭疽抗原特异性B细胞 感染者(在2001年生物恐怖袭击期间感染)，皮肤炭疽病例，以及 AVA接种人类志愿者，并产生一组分泌B细胞的抗炭疽抗体 这些群体中的每一个都有杂交瘤。来自这些杂交瘤的单抗将被研究 它们的炭疽蛋白专一性、结合特性和中和特性。 此外，我们建议从天花中分离和鉴定天花特异性B细胞杂交瘤。 疫苗(Dryvax)免疫的个体。 从这些杂交瘤中获得的单抗(MAbb)应该是治疗 了解抗体介导的对这两种病原体的保护，这两种病原体都是主要关注的 作为生物恐怖主义特工。此外，人抗炭疽中和单抗可能是一种来源 产生大量中和抗体用于未接种疫苗的受试者被动免疫 暴露于吸入性炭疽热。产生杂交瘤的人天花中和单抗可能是一种 用于未接种疫苗被动免疫的大量中和天花抗体的来源 暴露于天花的受试者。

Historically it has been very difficult to generate IgG antibody secreting human immortalized B cells that produce significant amounts of antibody. This has been a major stumbling block to the study of human B cell immunology, and the understanding of human neutralizing antibodies. Additionally, neutralizing antibodies can be valuable therapeutic agents. It has recently been demonstrated that human hybridomas can be made that secrete substantial amounts of antibodies, using the human myeloma cell line Karpas 707H. Using this new technology, we propose to isolate anthrax antigen-specific B cells from inhalation anthrax infected human subjects (infected during the bioterrorism attacks of 2001), cutaneous anthrax cases, and AVA vaccinated human volunteers, and generate a panel of anti-anthrax antibody secreting B cell hybridomas from each of these groups. Monoclonal antibodies from these hybridomas will be studied for their anthrax protein specificity, binding characteristics, and neutralization properties. In addition, we propose to isolate and characterize smallpox-specific B cell hybridomas from smallpo vaccine (Dryvax) immunized individuals. Monoclonal antibodies (mAbs) obtained from these hybridomas should serve as invaluable reagents for understanding antibody-mediated protection against these two pathogens, which are both of major concern as bioterrorism agents. Additionally, human anti-anthrax neutralizing mAbs may serve as a source for producing large quantities of neutralizing antibodies for passive immunization of non-vaccinated subjects exposed to inhalation anthrax. Human smallpox neutralizing mAb producing hybridomas may serve as a source for producing large quantities of neutralizing smallpox antibodies for passive immunization of nonvaccinated subjects exposed to smallpox.