Propagation Enhancement of Chimeric Lentiviral Vaccines

描述(由申请人提供)：传播嵌合粒子疫苗(PCP)是开发有效的HIV疫苗的有希望的候选者，因为它们有可能诱导类似于减毒活疫苗的免疫，而没有相关的安全问题。复制的颗粒疫苗将表达慢病毒Gag和Env，以诱导保护性中和抗体和抗HIV/AIDS的细胞免疫。Gag和Env由VEE复制子基因组表达，形成含有非整合、非致病、复制、嵌合的VEE/慢病毒基因组的颗粒。然而，传播的嵌合颗粒没有优先包装基因组RNA的特定机制。目前，疫苗产生的颗粒混杂地将任何可用的RNA包装在受感染细胞的细胞质中。因此，本研究的目的是增强Gag/Env PCP对基因组RNA的特异性包裹，从而提高疫苗的最终免疫原性。PCP疫苗将经过修改，以包含甲病毒和慢病毒包裹增强信号，并对颗粒形成、基因组RNA的特异性结合和包裹以及复制能力进行评估。

DESCRIPTION (provided by applicant): Propagating chimeric particle vaccines (PCP) are promising candidates for the development of an effective vaccine against HIV, because they have the potential to induce immunity similar to live-attenuated vaccines without the associated safety concerns. Replicating particle-based vaccines will be generated to express lentiviral Gag and Env for the induction of protective neutralizing antibody and cellular immunity against HIV/AIDS. Gag and Env are expressed from a VEE replicon genome and form particles that contain a non-integrating, nonpathogenic, replicating, chimeric VEE/lentiviral genome. However, the propagating chimeric particle does not have a specific mechanism to preferentially package genomic RNA. Currently, the particles produced by the vaccine promiscuously package any available RNA within the cytoplasm of the infected cell. Therefore, the goal of this research is to enhance the specific encapsidation of genomic RNA by Gag/Env PCP, thereby improving the ultimate immunogenicity of the vaccine. The PCP vaccine will be modified to contain alphaviral and lentiviral encapsidation enhancement signals and evaluated for particle formation, specific binding and encapsidation of genomic RNA as well as replication competency.