Immune Responses to VSV/HIV/SIV Hybrids in Macaques

活病毒疫苗传统上提供了最有效的保护，防止病毒感染。等 疫苗诱导强烈的细胞和体液免疫应答，这是由于高水平的细胞内合成 抗原在很长一段时间内。表达蛋白质的活减毒水泡性口炎病毒（VSV）载体 在动物模型中是非常有效的疫苗。表达HIV-1 Env和SIV的VSV载体 在恒河猴模型中，Gag蛋白已被证明能有效预防艾滋病。第一 用于猕猴的VSV载体的产生从下游位置表达SI-IIV gag和env基因 在VSV基因组中。虽然这些载体表达了大量的SHIV蛋白，但新的载体 现在已经开发出允许从第一个表达位点甚至更大的蛋白质表达， 在VSV基因组中的位置。从第一个位置表达的蛋白质是细胞中产生的主要蛋白质。 被感染的细胞本项目的主要目标是测试这些新载体在恒河猴中的有效性 猕猴，并包括Pol蛋白的表达以产生对另外的CTL表位的免疫应答。 免疫反应的强度将被定量跟踪并与以前的研究进行比较， 通过分析病毒载量峰值、CD 4 T细胞亚群和免疫原性， 计数、病毒载量设定点和艾滋病防护。优化的VSV载体表达系统将 还将用于第二项研究，以确定基于VSV的疫苗系统是否也可以在一个特定的环境中预防艾滋病。 使用SIV而不是SHIV89.6p进行激发。后面的一系列实验很重要，因为SIV 猕猴的感染更接近于人类的HIV感染。拟议的研究还将 从最初的赠款期开始，继续对7只感染SHIV的疫苗保护猕猴进行随访 确定疫苗保护的持久性

Live viral vaccines have traditionally offered the most effective protection against viral infections. Such vaccines induce strong cellular and humoral immune responses due to high level intracellular synthesis of antigens over extended periods. Live attenuated vesicular stomatitis virus (VSV) vectors expressing proteins of other viruses are highly effective vaccines in animal models. VSV vectors expressing HIV-1 Env and SIV Gag proteins have proven effective in protecting against AIDS in a rhesus macaque model. The first generation of VSV vectors used in macaques expressed SI-IIV gag and env genes from a downstream position in the VSV genome. Although these vectors expressed substantial amounts of SHIV proteins, new vectors have now been developed that allow even greater protein expression from an expression site in the first position in the VSV genome. Proteins expressed from the first position are the major proteins produced in infected cells. The major goal of this project is to test the effectiveness of these new vectors in rhesus macaques and to include expression of Pol protein to generate immune responses to additional CTL epitopes. The magnitude of the immune responses will be followed quantitatively and compared with previous studies, and the extent of protection from challenge will be monitored through analysis of peak viral loads, CD4 T cell counts, viral load set points, and protection from AIDS. The optimized VSV vector expression system will also be used in a second study to determine if the VSV-based vaccine system can also protect from AIDS in a challenge using SIV rather than SHIV89.6p. This later series of experiments is important because SIV infection of macaques more closely mimics HIV infection in humans. The proposed studies will also continue the follow up on the seven SHIV-infected, vaccine-protected macaques from the initial grant period to determine durability of vaccine protection