Bio-Nanoparticles for HIV Antigen Delivery

描述(由申请人提供)：有效的HIV-1疫苗很可能需要CTL诱导成分。到目前为止，只有重组腺病毒-5疫苗是这种成分的候选疫苗，但它面临着媒介免疫方面的重大问题，并具有未知的进入粘膜组织的能力。纳米颗粒作为疫苗载体提供了一些优势，但面临着免疫原性、致癌性和制造质量方面的问题。 这项提议探索使用由自体人类蛋白组成的生物纳米颗粒(“金库”)作为疫苗，这些纳米颗粒装载着HIV-1序列。已证明拱顶对CTL反应具有免疫原性，并可进入粘膜免疫系统。此外，它们是由通常在细胞质中发现的自身蛋白组成的，因此不应具有免疫原性或致癌性，而且易于制造，质量稳定。这两个目标是： 目的1：创建携带保守的HIV-1蛋白序列的靶向库； 目的2：证实系统免疫和粘膜免疫隔膜中的拱顶具有免疫原性。

DESCRIPTION (provided by applicant): It is likely that a CTL-eliciting component will be required for an effective HIV-1 vaccine. To date, only the recombinant adenovirus-5 vaccine has been a candidate for such a component, but it faced significant issues with vector immunity and had unknown capacity to access mucosal tissues. Nanoparticles offer some advantages as vaccine vectors, but face problems with immunogenicity, carcinogenicity, and manufacturing quality. This proposal explores the use of biological nanoparticles ("vaults") composed of autologous human proteins, loaded with HIV-1 sequences to serve as a vaccine. Vaults have been shown to be immunogenic for CTL responses and access the mucosal immune system. Additionally, they are composed of self-proteins that are normally found in the cytoplasm and therefore should not be immunogenic or carcinogenic, and are readily manufactured with consistent quality. The two aims will be: Aim 1: To create targeted vaults carrying conserved HIV-1 protein sequences; Aim 2: To confirm the immunogenicity of the vaults in systemic and mucosal immune compartments.