ANTIBODY FC AND HIV-1 INACTIVATION

抗体 FC 和 HIV-1 灭活

• 批准号: 2672873
• 负责人: PAUL W PARREN
• 金额: $ 12.17万
• 依托单位: SCRIPPS RESEARCH INSTITUTE, THE
• 依托单位国家: 美国
• 财政年份: 1996
• 资助国家: 美国
• 起止时间: 1996-07-01 至 2001-06-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/2672873
• 关键词: SCID mouse; antibody receptor; antigen antibody reaction; antiviral antibody; complement pathway; dendritic cells; human immunodeficiency virus 1; human tissue; immunoglobulin G; neutralizing antibody; passive immunization; point mutation; receptor binding; tissue /cell culture

DESCRIPTION: (Adapted from investigator's abstract) Potent HIV-1 neutralizing monoclonal antibodies have been isolated and are being developed for passive immunotherapy. It is assumed that neutralizing ability in vitro will provide a good indication for anti-viral efficacy in vivo. To what extent antibody-mediated functions associated with Fc region contribute to viral clearance is however unclear. In particular, interactions with Fc- or complement receptors may potentiate neutralization or, under certain condition, potentiate infection. The particular type of receptor involved may have a profound effect on outcome of the interaction of virus-antibody complexes with effector cells. The role of Fc-mediated functions in HIV-1 clearance will be studied in detail by preparing a set of variants of the potent broadly HIV-1 neutralizing antibody IgG1 b12. These variants will have point-mutations introduced into their heavy chain constant domains targeted to specifically knock out selected effector mechanisms. Effects on HIV-1 inactivation by b12 will be studied in vitro and in vivo using primary isolates of HIV-1.

描述：（改编自研究者摘要）强效HIV-1 已经分离出中和性单克隆抗体， 用于被动免疫治疗 据推测， 在体外的能力将提供抗病毒功效的良好指示， vivo. 在何种程度上抗体介导的功能与Fc区相关 然而，对病毒清除的贡献尚不清楚。 特别是， 与Fc或补体受体的相互作用可增强中和作用 或者在某些情况下，加强感染。 的特定类型的 参与的受体可能对相互作用的结果产生深远的影响 病毒抗体复合物与效应细胞的结合。 Fc介导的作用 在HIV-1清除中的功能将通过制备一组 有效的广泛HIV-1中和抗体IgG 1 b12的变体。 这些 变异体将在其重链中引入点突变 靶向特异性敲除所选效应子的恒定结构域 机制等 将在体外研究b12对HIV-1灭活的影响 和使用HIV-1的原代分离物的体内试验。