Plantibodies and Plantibody Hybrids as HIV Microbicides

Plantibody 和 Plantibody 杂种作为 HIV 杀微生物剂

• 批准号: 6444303
• 负责人: Kevin John Whaley
• 金额: $ 30万
• 依托单位: EPICYTE PHARMACEUTICAL, 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/6444303
• 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(植物抗体)中产生人类抗体和抗体杂交物)满足 市场需要(低成本、大容量)的阴道杀菌剂 预防人类免疫缺陷病毒(HIV)的性传播。自.以来 艾滋病毒的性传播机制还不是很清楚， 植物体将发展成一系列单独或 协同作用可提供防止粘膜传播艾滋病毒的保护。 几种经过充分研究的抗gp160(2F5、2G12、4E10)的单抗 显示出广泛的体外中和活性，对初级分离物和 对灵长类动物的保护将在植物中产生。因为植物体杂交种可能 不太容易受到gp160变异性或表位可及性的影响，两个杂交 将在以下植物中制造：(A)PRO542，其用CD4取代结合 抗体支架的结构域；(B)sCD4-17b(与HIV单链抗体相连的CD4) 导致gp120的构象改变，从而使抗体结合域 与先前未暴露的保守表位相互作用。此外，一个 针对艾滋病毒共同受体CCR5(PRO140)的抗体将作为一种 植物抗体，以便对受体靶向策略进行评估。这些HIV病毒 植物抗体和植物抗体杂交体可以与植物抗体结合起来对抗 已经在植物中产生的其他性传播疾病病原体 由Epicyte提供广谱阴道保护。 拟议的商业应用：以植物为基础的生产系统提供了一个独特的机会，以成本提供大量保护性植物小体和植物小体杂交，从而使这项技术能够应用于防止广泛的传染性病原体的粘膜传播。