HUMAN MONOCLONAL ANTIBODIES TO CATEGORY A PATHOGENS

A 类病原体的人单克隆抗体

• 批准号: 7658456
• 负责人: ROBERT S MITTLER
• 金额: $ 26.11万
• 依托单位: EMORY UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2008
• 资助国家: 美国
• 起止时间: 2008-04-01 至 2009-03-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7658456
• 关键词: Anthrax Vaccines; Anthrax disease; Antibodies; Antibody-mediated protection; Antigens; B-Lymphocytes; Binding; Bioterrorism; Breathing; Categories; Cell Line; Characteristics; Cutaneous; DryVax vaccine; Human; Human Volunteers; Hybridomas; Immunoglobulin G; Immunology; Individual; Monoclonal Antibodies; Multiple Myeloma; Passive Immunization; Property; Proteins; Reagent; Smallpox; Smallpox Vaccine; Source; Specificity; Therapeutic Agents; Vaccinated; human monoclonal antibodies; human subject; neutralizing antibody; neutralizing monoclonal antibodies; new technology; passive antibodies; pathogen

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.

从历史上看，产生分泌人类永生化 B 细胞的 IgG 抗体非常困难。 产生大量抗体。这是人类 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。此外，中和抗体 可以成为有价值的治疗剂。最近的研究表明，人类杂交瘤可以 使用人类骨髓瘤细胞系 Karpas 707H 制造出分泌大量抗体的药物。 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（2001 年生物恐怖主义袭击期间感染）、皮肤炭疽病例，以及 AVA给人类志愿者接种疫苗，并产生一组分泌抗炭疽抗体的B细胞 来自每一组的杂交瘤。来自这些杂交瘤的单克隆抗体将被研究 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和鉴定天花特异性 B 细胞杂交瘤。 疫苗（Dryvax）已免疫个体。 从这些杂交瘤中获得的单克隆抗体 (mAb) 应作为宝贵的试剂 了解抗体介导的针对这两种病原体的保护作用，这两种病原体都是人们主要关注的问题 作为生物恐怖主义代理人。此外，人类抗炭疽中和单克隆抗体可作为 产生大量中和抗体，用于未接种疫苗的受试者的被动免疫 暴露于吸入性炭疽。产生人天花中和单克隆抗体的杂交瘤可作为 生产大量中和天花抗体的来源，用于未接种疫苗的被动免疫 暴露于天花的受试者。