Bio-Nanoparticles for HIV Antigen Delivery

描述（由申请方提供）：有效的HIV-1疫苗可能需要CTL诱导成分。迄今为止，只有重组腺病毒-5疫苗是这种组分的候选者，但它面临着载体免疫的重大问题，并且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，但面临免疫原性、致癌性和制造质量的问题。 该提案探索了使用由自体人类蛋白质组成的生物纳米颗粒（“拱顶”），加载HIV-1序列作为疫苗。穹窿已被证明对CTL应答具有免疫原性并进入粘膜免疫系统。此外，它们由通常在细胞质中发现的自身蛋白组成，因此不应具有免疫原性或致癌性，并且易于以一致的质量生产。这两个目标是： 目的1：构建携带HIV-1保守蛋白序列的靶向库; 目的2：证实穹窿在全身和粘膜免疫区室中的免疫原性。

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.