GB VIRUS C INFECTION OF MACAQUES: AN HIV VACCINE MODEL

该子项目是利用NIH/NCRR资助的中心赠款提供的资源的许多研究子项目之一。子项目和研究者（PI）可能从另一个NIH来源获得主要资金，因此可以在其他CRISP条目中表示。所列机构为中心，不一定是研究者所在机构。估计有4 000万人感染艾滋病毒，仅在2001年就造成300多万人死亡。通过疫苗接种预防HIV感染的努力尚未成功，这在很大程度上是因为常规疫苗构建体的有限功效以及对活病毒载体安全性的担忧。为了克服这些限制，我们建议使用GB病毒C，最近发现的黄病毒，作为HIV疫苗的重组载体。GBV-C具有理想的重组载体的许多特征，包括：安全性9没有已知的人类疾病与这种病毒有关，这种病毒在约2%的健康献血者中引起持续感染，尽管通过输血传播，但在献血中没有进行筛查。实验模型（存在GBV-C的细胞系，并且已经制备了感染性克隆。此外，有证据表明，猕猴，艾滋病毒疫苗研究的最重要的动物模型，对GBV-C是允许的。和免疫原性（由于病毒感染人类数月/数十年，因此预期强的细胞和体液免疫应答）。因此，该试验补助金的目的是进行扩大工作所需的初步研究，以开发GBV-C作为HVI疫苗的重组载体。我们最初的目的是确认恒河猴可以感染GBV-C，表征感染的自然史，并暂时检查组织嗜性。

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. An estimated 40 million persons are infected with HIV, which caused more than three million deaths in 2001 alone. Efforts to prevent HIV infection by vaccination have no been successful, in large part because of the limited efficacy of conventional vaccine constructs as well as concerns with the safety of live virus vectors. To overcome these limitations, we propose using GB virus C, a recently discovered flavivirus, as a recombinant vector for HIV vaccines. GBV-C has many features of an ideal recombinant vector including: Safety 9No known human disease is associated with this virus which causes persistent infection in ~2% of healthy blood donors and, although transmitted by transfusion, is not screened for in donations.); experimental models (Cell lines exist for GBV-C and an infectious clone has already been made. In addition, there is evidence that macaques, the most important animal model for HIV vaccine research, are permissive for GBV-C.); and immunogenicity (Strong cellular and humoral immune responses are expected since the virus infects humans for months/decades.). Thus, the purpose of this pilot grant is to conduct preliminary studies required for expanded work to develop GBV-C as a recombinant vector for HVI vaccines. Our initial aims are to confirm that rhesus macaques can be infected with GBV-C, to characterize the natural history of infection, and to provisionally examine tissue tropism.