HERPESVIRUS VECTORS AS VACCINES FOR SIMIAN IMMUNODEFICIENCY VIRUS

有充分的理由相信，发展一种有效的 在人类身上接种HIV-1疫苗将是一项非常困难的任务。这个 预测实现针对艾滋病毒和SIV的疫苗保护的难度 在动物模型中进行的疫苗试验或多或少证实了这一点。我们的 实验室最近展示了令人印象深刻的保护作用 SIV AS的活性减毒、nef缺失和倍增缺失的衍生物 疫苗。我们尝试过的其他疫苗方法都没有取得成功。 与我们在现场看到的保护效果相差无几- 弱化进场。虽然我们不知道 保护，持续的抗原表达导致持续的 感染可能是一个关键因素。我们将调查坚持不懈 疱疹病毒感染导致的载体表达可以匹配 保护效力的活体减毒方法。具备复制能力 阿尔法疱疹病毒、单纯疱疹病毒和伽马病毒的菌株 将对表达SIV抗原的疱疹病毒进行检测 它们在SIV/恒河猴身上产生保护效力的能力 模特。利用结构性SV的疱疹病毒的特性 启动子与内源性疱疹病毒启动子的载体表达将 进行比较，因为可能需要受调控的疱疹病毒启动子来治疗高发 级别持之以恒。我们还将分析复制能力- 表达SIV抗原的缺陷型单纯疱疹病毒载体 复制缺陷的SIV可引起免疫反应和保护。这个 拟议的研究预计将提供关于以下类型的基本信息 实现可靠疫苗所需的免疫和免疫反应 保护。

There are good reasons for believing that development of an effective vaccine against HIV-1 in humans is going to be a very difficult task. The predicted difficulty in achieving vaccine protection against HIV and SIV has more or less been borne out by vaccine trials in animal models. Our laboratory has recently demonstrated impressive protective effects of live-attenuated, nef-deleted and multiply-deleted derivatives of SIV as vaccines. No other vaccine approach that we have tried has come even remotely close to the protective effects that we have seen with the live- attenuated approach. Although we do not know the basis for the protection, continued antigen expression resulting from persistent infection may be a key factor. We will investigate whether persistent vectored expression resulting from herpesvirus infection can match the live-attenuated approach for protective efficacy. Replication competent strains of the alpha herpesvirus, herpes simplex virus, and the gamma herpesvirus, herpesvirus saimiri, that express SIV antigens will be tested for their ability to elicit protective efficacy in the SIV/rhesus monkey model. The properties of herpesviruses that utilize a constitutive SV promoter vs endogenous herpesviral promoters for vectored expression will be compared since a regulated herpesvirus promoter may be needed for high level persistence. We will also analyze the ability of replication- defective herpes simplex virus vector expressing SIV antigens and of replication-defective SIV to elicit immune responses and protection. The proposed studies are expected to provide basic information on the types of immunization and immune responses that are needed to achieve solid vaccine protection.