ANTIBODY EFFECTOR FUNCTION IN PROTECTION AGAINST HIV-1

这个子项目是许多研究子项目中利用 资源由NIH/NCRR资助的中心拨款提供。子项目和 调查员(PI)可能从NIH的另一个来源获得了主要资金， 并因此可以在其他清晰的条目中表示。列出的机构是 该中心不一定是调查人员的机构。 目的：改进体外检测方法，以预测对HIV暴露提供最佳益处的抗体反应类型。 我们希望测试的总体假设是，抗体效应器功能对于预防HIV攻击至关重要，我们可以剖析体内重要的关键功能，我们可以利用这一知识来改进体外分析，以预测将提供最佳抗HIV暴露益处的抗体反应类型。 该项目包括两个主要实验： 在目前的研究中，我们使用重组人免疫缺陷病毒(SIV)感染恒河猴模型来了解两种不同功能的保护性抗体在人类抗HIV感染中的作用。在第一项研究中，我们将确定保护性抗体在杀死和消除受感染细胞方面的作用。我们将用两种不同但密切相关的抗体来治疗两组动物，这两种抗体经过基因工程改造，可以很好地发挥杀戮或消除功能。我们将比较这两组动物以及其他三组动物对病毒血症的控制情况。后三组动物中的一组将不接受任何抗体治疗，另一组将接受兼具两种功能的抗体治疗，第三组将接受具有保护活性但缺乏杀灭活性且也不利于消除感染细胞的抗体治疗。 在第二组实验中，我们询问如果上述两种保护性抗体中的一种功能得到增强，对SHV感染的保护是否会更好。为了解决这个问题，我们将用两种不同但密切相关的抗体来治疗两组动物，这些抗体经过基因工程，只在增强的水平上执行这两种功能中的一种。我们将比较两组动物中病毒血症的控制情况，以及不接受任何抗体治疗或将接受同时具有两种功能的抗体治疗的动物组之间的病毒血症控制情况。 子项目进展，实验1：我们已经选择了将参与第一个实验的动物。我们计划在2010年3月开始研究。 该项目使用WNPRC研究服务和动物服务。

This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. The subproject and investigator (PI) may have received primary funding from another NIH source, and thus could be represented in other CRISP entries. The institution listed is for the Center, which is not necessarily the institution for the investigator. Objective: To improve in vitro assays to predict the types of antibody responses that will provide optimal benefit against HIV exposure. The overarching hypotheses that we wish to test is that antibody effector function is critical to protection against HIV challenge, that we can dissect the crucial functions important in vivo and that we can use this knowledge to improve in vitro assays to predict the types of antibody responses that will provide optimal benefit against HIV exposure. This project includes two main experiments: In the current studies we use the recombinant Simian Human Immunodeficiency Virus (SHIV) infected-Rhesus macaque model to understand the role of two different functions of the protective antibodies against HIV infection in humans. In the first study we will determine the role of the protective antibodies in killing and eliminating the infected cells. We will treat two groups of animals with two different, but closely related antibodies that were genetically engineered to perform either the killing or the eliminating function well. We will compare the control of viremia in these two groups of animals and between three other groups of animals. One of the latter three groups of animals will not be treated with any antibody, the other group will be treated with an antibody that has both functions, and the third group will be treated with an antibody that has protective activity, but lacks killing activity and does not facilitate the eliminating of the infected cells either. In a second set of experiments we ask whether the protection against SHIV infection is better if one of the two above mentioned functions of the protective antibodies is enhanced. To address this issue we will treat two groups of animals with two different, but closely related antibodies that were genetically engineered to perform just one of these two functions at an enhanced level. We will compare the control of viremia in the two groups of animals and between groups of animals that will not be treated with any antibody, or will be treated with an antibody that has both functions at a normal level. Subproject Progress, Experiment 1: We have selected animals that will participate in the first experiment. We plan to start the studies in March of 2010. This project uses WNPRC Research Services and Animal Services.