ANTIBODY FC AND HIV-1 INACTIVATION

描述：(改编自研究人员摘要)有效的HIV-1 中和性单抗已经被分离出来，并正在进行 为被动免疫治疗而开发。据推测，中和 体外能力将为抗病毒疗效提供良好的指征。 活着。抗体在多大程度上与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能增强中和作用 或者，在某些情况下，会加剧感染。特定类型的 参与的受体可能会对相互作用的结果产生深远的影响 病毒抗体与效应细胞的复合体。Fc-介导的作用 将详细研究HIV-1清除过程中的功能，准备一套 有效的广谱HIV-1中和抗体IgG1B12的变体。这些 变种将在其重链中引入点突变 以特定敲除选定效应器为目标的恒定域 机械装置。将在体外研究B12对HIV-1灭活的影响 并在体内使用HIV-1的初级分离株。

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.