WHICH ISOTYPE OF ECD4-IG MOST EFFECTIVELY SUPPRESSES VIRUS REPLICATION?

 描述（由申请人提供）：我们设计了一种合成抗体，可100%中和HIV毒株。这种抗体是由HIV识别的CD 4和CCR 5部分构建的，被命名为“eCD 4-IG”。“我们研究计划的目标是最大限度地发挥其功效。对于我们的努力和整个领域来说，一个基本的问题是：哪种IgG同种型具有抑制病毒复制最重要的特性？为了回答这个问题，我们将消除IgG 2和IgG 3的问题特征，这些特征在历史上阻碍了它们作为人类治疗剂的使用，我们将比较恒河猴IgG 1、IgG 2和IgG 3形式的eCD 4-IG抑制猕猴中SIV复制的能力。最完全抑制病毒复制的eCD 4-IG同种型将推进人体临床试验。

 DESCRIPTION (provided by applicant): We have engineered a synthetic antibody that neutralizes 100% of HIV strains. This antibody is built from the parts of CD4 and CCR5 that are recognized by HIV, and is named "eCD4-Ig." The goal of our research program is now to maximize its efficacy. A fundamental question for our effort-and for the field as a whole-is: Which isotype of IgG has the properties that are most important for suppressing viral replication? To answer this question, we will eliminate problematic features of IgG2 and IgG3 that have historically presented a barrier to their use as therapeutics in humans, and we will compare the ability of rhesus IgG1, IgG2, and IgG3 forms of eCD4-Ig to suppress SIV replication in macaques. The isotype of eCD4-Ig that most completely suppresses viral replication will be advanced to human clinical trials.