EVALUATION OF DELIPIDATED LENTIVIRUSES AS MODE OF THERAPEUTIC IMMUNIZATION

这个子项目是许多研究子项目中的一个 由NIH/NCRR资助的中心赠款提供的资源。子项目和 研究者（PI）可能从另一个NIH来源获得了主要资金， 因此可以在其他CRISP条目中表示。所列机构为 研究中心，而研究中心不一定是研究者所在的机构。 该项目探讨了脂质耗尽的SIV和HIV作为SIV感染后自体治疗性免疫的模式的潜力。初步的非感染性研究已经使用HIV-1作为免疫恒河猴的模型，比较未操作的与溶剂处理的HIV产生的免疫应答。该研究的第二组在本日历年度完成，并使用了SIV慢性感染的恒河猴，SIV首先从恒河猴中分离，溶剂处理并在抗逆转录病毒治疗下重新接种。在治疗尝试之前和之后测量的抗病毒免疫应答和病毒载量表明，在这种自体免疫试验性实验之后，抗病毒控制得到适度但可识别的改善。已经启动了一项新的大规模研究，该研究将重复在中试实验中测试的策略，但在SIV感染后的早期时间点，由于动物免疫系统的损伤较低，这被认为可以产生更好的抗病毒控制。因此，对36只幼年恒河猴进行了筛选、分配并感染了1000 TCID 50的SIVmac 239。在急性病毒复制消退后，重复收集每只动物的血液以获得大量PBMC用于分离自体SIV。然后将来自每个测试受试者的SIV沉淀并脱脂。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，然后开始每月一次用自体脱脂SIV或对照PBS进行一系列连续3次腹股沟内淋巴结免疫接种。完成这些免疫接种后，将停止ART，并监测病毒载量和抗病毒免疫应答。

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 explores 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.