SINGLE CYCLE SIV PARTICLES NOVEL VACCINE STRATEGY

我们在这个提案中的目标是构建和测试一个单周期 SIV（SC-SIV）颗粒作为抗原来源用于产生和 在恒河猴中最大化针对SIV感染的免疫应答 猕猴。 这一新战略的独特之处在于， 病毒复制只允许经历一个周期， 避免与灭活整体相关的潜在风险 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， 从而允许刺激细胞毒性T淋巴细胞（CTL）， vivo. 因此，这种疫苗特别适合 吸引人的原因是它最接近于活的减毒病毒 一种对SIV提供高度保护的疫苗 猕猴的感染，同时消除与 持续的病毒复制 通过多次引入这种 单循环颗粒进入恒河猴，希望 粒子会产生免疫反应 在幅度和频谱上模仿在 感染SIVmac 239的猕猴nef和SIVmac 239？3种病毒。 允许从头合成病毒蛋白质，同时限制病毒 因此，从受感染的细胞扩散是 新的疫苗策略。 树突状细胞（Dendritic Cells，DCs） 抗原递呈细胞也是有效的引发剂， 免疫系统的刺激物。 最近的事态发展使它 可以直接从外周血中分离大量的纯DC， 血单核细胞 利用这些新的发展， 我们会将树突状细胞纳入免疫方案， SC-SIV的免疫原性和抗原性 SIV特异性体液和CTL 反应将进行研究，以评估这一新的有效性 疫苗和免疫战略。 资助NIH（R21 AI 42669） 出版物

Our goal in 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 SIVmac239?nef and SIVmac239?3 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, we will include DCs in our 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. FUNDING NIH (R21 AI42669) PUBLICATIONS None