Plantibodies and Plantibody Hybrids as HIV Microbicides

Plantibody 和 Plantibody 杂种作为 HIV 杀微生物剂

• 批准号: 6854214
• 负责人: Kevin John Whaley
• 金额: $ 18.95万
• 依托单位: MAPP BIOPHARMACEUTICAL, INC.
• 依托单位国家: 美国
• 财政年份: 2002
• 资助国家: 美国
• 起止时间: 2002-09-01 至 2004-08-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6854214
• 关键词: CD4 molecule; HIV envelope protein gp120; antiAIDS agent; antiviral agents; conformation; drug design /synthesis /production; hybrid antibody; immunologic substance development /preparation; monoclonal antibody; mucosal immunity; plant extracts; virus receptors

DESCRIPTION: (Provided by Applicant) The objective of this project is to produce human antibodies and antibody hybrids in plants (plantibodies)) to meet the market needs (low cost, large capacity) of a vaginal microbicide for preventing the sexual transmission of human immunodeficiency virus (HIV). Since the mechanisms of sexual transmission of HIV are not well understood, plantibodies will be developed to a range of targets that individually or synergistically may provide protection against mucosal HIV transmission. Several well-studied monoclonal antibodies to gp160 (2F5, 2G12, 4E10) that have demonstrated broad neutralizing activity in vitro against primary isolates and protection in primates will be produced in plants. Since plantibody hybrids may be less susceptible to gp160 variability or epitope accessibility, two hybrids will be manufactured in plants: (a) PRO542 which has CD4 replacing the binding domain of the antibody scaffold; (b) sCD4-17b (CD4 linked to an HIV scFv) causes a conformation change in gp120 that enables the antibody binding domain to interact with a previously unexposed, conserved epitope. In addition, an antibody to CCR5 (PRO140), the HIV co-receptor, will be produced as a plantibody so that a receptor-targeted strategy can be evaluated. These HIV plantibodies and plantibody hybrids can be combined with plantibodies against other sexually transmitted disease pathogens already being produced in plants by Epicyte for broad-spectrum vaginal protection. PROPOSED COMMERCIAL APPLICATION: Plant-based production systems offer a unique opportunity to provide large quantities of protective plantibodies and plantibody hybrids at a cost that enables the application of this technology to preventing mucosal transmission of a wide range of infectious pathogens.

描述：（申请人提供）本项目的目标是 在植物中产生人抗体和抗体杂交体（plantibodies）），以满足 市场需要（低成本、大容量）阴道杀微生物剂 预防人类免疫缺陷病毒（HIV）的性传播。以来 艾滋病毒的性传播机制尚不清楚， plantibodies将被开发成一系列的目标， 可以协同地提供针对粘膜HIV传播的保护。 几种研究充分的抗gp 160单克隆抗体（2F 5，2G 12，4 E10）， 在体外对原代分离株表现出广泛的中和活性， 灵长类动物的保护作用将在植物中产生。由于植物体杂交体可能 对gp 160变异性或表位可及性较不敏感，两个杂交体 将在工厂生产：（a）PRO542，其具有CD 4替代结合 抗体支架的结构域;（B）sCD 4 - 17 B（与HIV scFv连接的CD 4） 引起GP 120的构象变化 与先前未暴露的保守表位相互作用。此外，一个 HIV共受体CCR 5（PRO 140）的抗体将作为 plantibody，以便可以评估受体靶向策略。这些HIV 植物体和植物体杂交体可以与植物体组合， 其他已经在植物中产生的性传播疾病病原体 用于广谱阴道保护 拟定商业应用：基于植物的生产系统提供了一个独特的机会，以提供大量的保护性植物体和植物体杂交体，其成本使得该技术能够应用于预防各种感染性病原体的粘膜传播。