ANTIBODY EFFECTOR FUNCTION IN PROTECTION AGAINST HIV-1

这个子项目是利用资源的许多研究子项目之一。 由NIH/NCRR资助的中心拨款提供。对子项目的主要支持 子项目的首席调查员可能是由其他来源提供的， 包括美国国立卫生研究院的其他来源。为子项目列出的总成本可能 表示该子项目使用的中心基础设施的估计数量， 不是由NCRR赠款提供给次级项目或次级项目工作人员的直接资金。 目的：确定保护性抗体在杀灭感染细胞中的作用。 此外，为了确定如果抗体的这些功能之一--杀死或消除受感染的细胞--得到增强，对SHIV感染的保护是否更好。(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。 对于第一个目标，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。 对于第二个目标，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改造，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。 进度： 我们已经进行了两个试点实验。在第一个中试实验中，我们在体内滴定了新的SHIV162P3病毒库，以确定我们将在主要实验中使用的攻击剂量。在第二个初步实验中，我们测定了抗体NFb12从血液到阴道腔的分泌动力学。NFb12抗体是广泛中和HIV抗体B12的变种。其Fc结构域已被修饰以增强ADCC和吞噬功能。我们已经开始了第二个实验，以确定抗体NFb12的中和能力。我们使用低浓度(1 mg/kg)的NFb12来应对重复的低剂量SHIV162P3挑战。 这项研究使用了动物服务、CPI和病毒学与免疫学服务。 出版物： 没有。

This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. Primary support for the subproject and the subproject's principal investigator may have been provided by other sources, including other NIH sources. The Total Cost listed for the subproject likely represents the estimated amount of Center infrastructure utilized by the subproject, not direct funding provided by the NCRR grant to the subproject or subproject staff. Objective: To determine the role of the protective antibodies in killing and eliminating the infected cells. Also, to determine whether the protection against SHIV infection is better if one of these functions of antibodies -- either killing or eliminating infected cells -- is enhanced. (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. For the first objective, 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. For the second objective, 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. PROGRESS: We have performed two pilot experiments. In the first pilot experiment, we titrated the new SHIV162P3 virus stock in vivo to determine the challenge dose that we will use in the main experiments. In the second pilot experiment, we determined the secretion kinetics of antibody NFb12 from the blood into the vaginal lumen. NFb12 antibody is a variant of the broadly neutralizing HIV antibody b12. Its Fc domain has been modified to enhance ADCC and phagocytosis. We have started the second experiment to determine the neutralization capabilities of antibody NFb12. We use a low concentration (1 mg/kg) of infused NFb12 against repeated low dose SHIV162P3 challenges. This research used Animal Services, CPI, and Virology & Immunology Services. PUBLICATIONS: None.