SINGLE CYCLE SIV PARTICLES--A NOVEL VACCINE STRATEGY

描述（改编自申请人的摘要）：本提案的目标 是构建和测试单循环SIV（SC-SIV）粒子作为 用于产生和最大化针对SIV的免疫应答的抗原 恒河猴的感染。 这部小说的独特之处在于 策略是病毒复制只允许经历一个单一的 循环，从而避免与失活的 全病毒疫苗或减毒活病毒疫苗。 另外这款 复制的单循环性质允许一定程度的从头开始 一旦颗粒进入靶细胞，病毒蛋白的合成， 允许在体内刺激细胞毒性T淋巴细胞（CTLS）。 这种类型 因此，疫苗候选人特别有吸引力，因为它最 非常类似于减毒活病毒疫苗， 保护猕猴免受SIV感染的程度，同时消除 与持续病毒复制相关的风险。 由多个 将这种单循环粒子引入恒河猴， 希望这些粒子能产生免疫反应， 在幅度和频谱上充分模拟保护性反应 在被SlVmac 239 dnef和SlVmac 239 d3病毒感染的猕猴中观察到。 允许从头合成病毒蛋白，同时限制病毒传播 因此，从受感染的细胞中提取的蛋白质是这种新的 疫苗战略。 树突状细胞（Dendritic cells，DCs）是一种特异性的抗原提呈细胞 细胞，也是免疫系统的有效引发剂和刺激剂。 最近的发展使分离大量的纯 DC直接来自外周血单个核细胞。 利用 这些新的发展，申请人计划将区议会纳入其 免疫方案，以增加SC-SIV的感染性和抗原性。 将研究SIV特异性体液和CTL应答，以评估SIV的免疫应答。 这种新型疫苗和免疫策略的有效性。

DESCRIPTION (adapted from applicant's abstract): The goal of this proposal is to construct and test a single-cycle SIV (SC-SIV) particle as a source of antigen for generating and maximizing an immune response against SIV infection in the rhesus macaque. The unique characteristic of this novel strategy is that viral replication is only allowed to undergo a single cycle, thereby avoiding the potential risks associated with an inactivated whole virus vaccine or a live attenuated virus vaccine. In addition, this single-cycle nature of replication allows a certain degree of de novo synthesis of viral proteins once the particle enters target cells, thereby allowing stimulation of cytotoxic T lymphocytes (CTLS) in vivo. This type of vaccine candidate is, therefore, particularly appealing because it most closely resembles the live attenuated virus vaccine that provides a high degree of protection against SIV infection in macaques, while eliminating the risks associated with persistent viral replication. By multiple introductions of this single-cycle particle into rhesus macaques, it is hoped that the particles will generate an immune response that would sufficiently mimic in magnitude and spectrum the protective responses observed in macaques infected by the SlVmac239dnef and SlVmac239d3 viruses. Allowing de novo synthesis of viral proteins while limiting viral spread from the infected cell is, therefore, the central component of this new vaccine strategy. Dendritic cells (DCs) are specialized antigen presenting cells and are also potent initiators and stimulators of the immune system. Recent developments have made it possible to isolate large numbers of pure DCs directly from peripheral blood mononuclear cells. Taking advantage of these new developments, the applicants plan to include DCs in their immunization regimen to increase the infectivity and antigenicity of SC-SIV. SIV-specific humoral and CTL responses will be studied to evaluate the effectiveness of this novel vaccine and immunization strategy.