Propagation Enhancement of Chimeric Lentiviral Vaccines

描述（由申请方提供）：嵌合颗粒疫苗（PCP）是开发HIV有效疫苗的有希望的候选疫苗，因为它们具有诱导类似于减毒活疫苗的免疫力的潜力，而没有相关的安全性问题。将产生基于复制颗粒的疫苗，以表达慢病毒Gag和Env，用于诱导针对HIV/AIDS的保护性中和抗体和细胞免疫。Gag和Env由VEE复制子基因组表达，并形成含有非整合、非致病性、复制型嵌合VEE/慢病毒基因组的颗粒。然而，繁殖嵌合颗粒不具有优先包装基因组RNA的特定机制。目前，由疫苗产生的颗粒混杂地包装感染细胞的细胞质内的任何可用的RNA。因此，本研究的目的是增强Gag/Env PCP对基因组RNA的特异性修饰，从而提高疫苗的最终免疫原性。将对PCP疫苗进行修饰，使其含有甲病毒和慢病毒的腺苷酸化增强信号，并对颗粒形成、基因组RNA的特异性结合和腺苷酸化以及复制能力进行评价。

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.