HERPESVIRUS VECTORS AS VACCINES FOR SIMIAN IMMUNODEFICIENCY VIRUS

有充分的理由相信，发展有效的 在人类中研制HIV-1疫苗将是一项非常艰巨的任务。 的 预计难以实现针对艾滋病毒和SIV的疫苗保护 已经或多或少地被动物模型的疫苗试验所证实。 我们 实验室最近证明了令人印象深刻的保护作用， SIV的减毒活的、nef缺失的和多重缺失的衍生物， 疫苗。 我们尝试过的其他疫苗方法都没有达到平衡 与我们在现场看到的保护效果相差甚远， 弱化的方法。 虽然我们不知道的基础， 保护，持续的抗原表达导致持续的 感染可能是关键因素。 我们将调查是否持续 由疱疹病毒感染引起的载体表达可以匹配 保护功效的减活方法。 复制能力的 α疱疹病毒株、单纯疱疹病毒株和γ疱疹病毒株 将测试疱疹病毒、松鼠猴疱疹病毒、表达SIV抗原 它们在SIV/恒河猴中引起保护功效的能力 模型 利用组成型SV的疱疹病毒的特性 用于载体表达的启动子与内源性疱疹病毒启动子将 因为高表达可能需要调节的疱疹病毒启动子， 水平持久性。 我们还将分析复制的能力- 表达SIV抗原的缺陷型单纯疱疹病毒载体， 复制缺陷型SIV以引发免疫应答和保护。 的 预计拟议的研究将提供关于各种类型的基本信息， 获得固体疫苗所需的免疫和免疫应答 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.