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 是构建和测试单周SIV(SC-SIV)粒子作为 用于产生和最大化针对SIV的免疫反应的抗原 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次 循环，从而避免与未激活的 全病毒疫苗或减毒活疫苗。此外，这一点 复制的单周期特性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，从而 允许在体内刺激细胞毒性T淋巴细胞(CTL)。这种类型 因此，候选疫苗的最具吸引力是因为它最 与减毒活病毒疫苗非常相似，它提供了高度的 猕猴对SIV感染的保护程度，同时消除 与持续病毒复制相关的风险。乘以多个 将这种单周期粒子引入恒河猴体内，它是 希望这些粒子能产生一种免疫反应 在大小和频谱上充分模拟保护性反应 在感染SlVmac239dnef和SlVmac239d3病毒的猕猴身上观察到。 允许病毒蛋白质从头合成，同时限制病毒传播 因此，来自受感染细胞的是这一新的 疫苗战略。树突状细胞(DC)是一种特殊的抗原提呈细胞。 细胞，也是免疫系统的有力启动者和刺激者。 最近的发展使分离大量纯净的 DC直接来自外周血单核细胞。利用 这些新发展，申请人计划把区议会纳入他们的 免疫方案以增加SC-SIV的传染性和抗原性。 将研究SIV特异性体液和CTL反应，以评估 这种新型疫苗的有效性和免疫策略。

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.