HUMAN MONOCLONAL ANTIBODIES TO CATEGORY A PATHOGENS

历史上，产生分泌IgG抗体的人永生化B细胞是非常困难的， 产生大量的抗体这一直是人类B细胞研究的主要障碍 免疫学，以及对人类中和抗体的理解。另外，中和抗体 可以是有价值的治疗剂。最近已经证明，人杂交瘤可以是 使用人类骨髓瘤细胞系Karpas 707 H， 利用这项新技术，我们建议从吸入性炭疽中分离炭疽抗原特异性B细胞 受感染的人类受试者（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，并产生一组分泌抗炭疽抗体的B细胞 杂交瘤细胞。将研究来自这些杂交瘤的单克隆抗体， 它们的炭疽蛋白特异性、结合特性和中和特性。 此外，我们建议从小痘病毒中分离并鉴定小痘病毒特异性B细胞杂交瘤。 疫苗（Dryvax）免疫个体。 从这些杂交瘤中获得的单克隆抗体（mAb）应该作为无价的试剂， 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问题 生物恐怖分子此外，人抗炭疽中和mAb可以作为抗炭疽的来源。 产生大量中和抗体用于未接种受试者的被动免疫 吸入性炭疽热产生人天花中和mAb的杂交瘤可作为一种抗天花病毒的药物。 用于产生大量中和天花抗体的来源， 接触过天花的人

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.