DELIPIDATED LENTIVIRUSES AS THERAPEUTIC IMMUNIZATION POST SIV INFECTION

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。 本项目研究SIV感染后脂质耗尽的SIV和HIV作为自体治疗性免疫的可能性。初步的非传染性研究已经使用HIV-1作为免疫恒河猴的模型，比较了未经处理和溶剂处理的HIV产生的免疫反应。这项研究的第二部分在本历年完成，使用了长期感染SIV的恒河猴，从这些恒河猴中首次分离出SIV，进行了溶剂治疗，并在抗逆转录病毒治疗下重新给予治疗。在治疗尝试前后测量的抗病毒免疫反应和病毒载量表明，在这种自体免疫试点实验之后，抗病毒控制得到了适度但可识别的改善。一项新的大规模研究已经启动，将重复在试点实验中测试的策略，但在SIV感染后的早期时间点，这被认为可以产生更好的抗病毒控制，这要归功于动物免疫系统的较低损害。因此，对36只幼年恒河猴进行了筛查、分配并感染了SIVmac239的1000个TCID50。在急性病毒复制结束后，重复采集每只动物的血液，以获得大量的PBMC，用于分离自体SIV。然后对每个测试对象的SIV进行制粒和脱脂。这些动物目前正在接受抗逆转录病毒治疗(ART)，以降低病毒载量，然后开始一系列连续3次的腹股沟内淋巴结免疫接种，每隔一个月用脱脂的自体SIV或对照PBS进行免疫。在完成这些免疫接种后，将停止抗逆转录病毒治疗，并监测病毒载量和抗病毒免疫反应。

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. This project studies the potential of lipid depleted SIV and HIV as a mode of autologous therapeutic immunization post SIV infection. Preliminary non-infectious studies have used HIV-1 as a model to immunize rhesus macaques comparing unmanipulated versus solvent treated HIV generated immune responses. A second arm of the study was completed during this calendar year and has used chronically SIV infected rhesus macaques from which SIV was first isolated, solvent treated and readministered under antiretroviral therapy. Antiviral immune responses and viral loads measured before and after the therapeutic attempt suggested modest but identifiable improvement of antiviral control following such autologous immunization pilot experiment. A new large scale study has been initiated that will repeat the strategy tested in the pilot experiment but at early time points post SIV infection which is reasoned to generate better antiviral control thanks to lower impairment of the animal's immune system. Therefore, 36 juvenile rhesus macaques have been screened, assigned and infected with 1000 TCID50 of SIVmac239. Following resolution of the acute viral replication, each animal's blood was collected repetitively to obtain large numbers of PBMC for the isolation of autologous SIV. The SIV from each test subject was then pelleted and delipidated. The animals are currently undergoing antiretroviral therapy (ART) to lower viral loads before initiating a series of 3 consecutive intra inguinal lymph node immunizations with autologous delipidated SIV or control PBS at monthly intervals. Following completion of these immunizations, ART will be discontinued and viral loads and antiviral immune responses monitored.