Propagation Enhancement of Chimeric Lentiviral Vaccines

描述（由申请人提供）：繁殖嵌合颗粒疫苗（PCP）是开发有效抗HIV疫苗的有希望的候选疫苗，因为它们有可能诱导类似于减毒活疫苗的免疫，而没有相关的安全性问题。将产生复制颗粒疫苗，以表达慢病毒Gag和Env，以诱导保护性中和抗体和抗艾滋病毒/艾滋病的细胞免疫。Gag和Env从VEE复制子基因组中表达，并形成含有非整合、非致病性、复制、嵌合VEE/慢病毒基因组的颗粒。然而，繁殖嵌合粒子没有特定的机制来优先包装基因组RNA。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内。因此，本研究的目的是增强Gag/Env PCP对基因组RNA的特异性包封，从而提高疫苗的最终免疫原性。将对PCP疫苗进行修饰，使其含有甲型病毒和慢病毒囊化增强信号，并对颗粒形成、基因组RNA的特异性结合和囊化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.