DELIPIDATED LENTIVIRUSES AS THERAPEUTIC IMMUNIZATION POST SIV INFECTION

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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.