Bio-Nanoparticles for HIV Antigen Delivery

用于 HIV 抗原递送的生物纳米颗粒

• 批准号: 8653936
• 负责人: OTTO O YANG
• 金额: $ 19.25万
• 依托单位: UNIVERSITY OF CALIFORNIA LOS ANGELES
• 依托单位国家: 美国
• 财政年份: 2013
• 资助国家: 美国
• 起止时间: 2013-04-19 至 2015-03-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8653936
• 关键词: AIDS Vaccines; Adenoviruses; Amino Acid Sequence; Animal Model; Antigens; Attenuated; Autologous; Biological; Biological Assay; CD8B1 gene; Cells; Cytoplasm; Cytotoxic T-Lymphocytes; DNA; Development; Drug resistance; Eukaryotic Cell; Face; Fowlpox; Generations; HIV Antigens; HIV-1; Histocompatibility; Human; Immune; Immune system; Immunity; Infection; Infection prevention; Interferons; Left; Life; Mucous Membrane; Negative Staining; Pathway interactions; Peptide Sequence Determination; Peptides; Prevention; Preventive; Protein Subunits; Proteins; RNA Sequences; Recombinants; Ribonucleoproteins; Risk; Rome; Safety; Serotyping; Structure; Subunit Vaccines; Text; Thinking; Toxic effect; Transmission Electron Microscopy; Untranslated RNA; Vaccine Design; Vaccines; Vaccinia; Vaccinium; Viral; Viral Proteins; Viremia; Virus; Work; arm; carcinogenicity; immune activation; immunogenic; immunogenicity; killings; memory CD4 T lymphocyte; nanoparticle; neutralizing antibody; novel strategies; optimism; public health relevance; response; success; therapeutic vaccine; vaccine candidate; vector; vector vaccine; viral resistance

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.

描述（由申请人提供）：有效的HIV-1疫苗可能需要使用CTL的组件。迄今为止，只有重组腺病毒-5疫苗一直是这种成分的候选者，但它面临着载体免疫的重大问题，并且具有进入粘膜组织的不明能力。纳米颗粒作为疫苗向量具有一些优势，但面临免疫原性，致癌性和制造质量的问题。 该提案探讨了由自体蛋白组成的生物纳米颗粒（“ Vaults”）的使用，并带有HIV-1序列作为疫苗。已证明保管库是CTL反应的免疫原性，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蛋白组成，因此不应具有免疫原性或致癌性，并且很容易以一致的质量制造。这两个目标将是： 目标1：创建携带保守的HIV-1蛋白序列的靶向穹顶； 目的2：确认全身和粘膜免疫室中保险库的免疫原性。