Bio-Nanoparticles for HIV Antigen Delivery

用于 HIV 抗原递送的生物纳米颗粒

基本信息

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
项目类别：
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

项目摘要

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 CTL 诱导成分。迄今为止，只有重组腺病毒 5 疫苗是此类成分的候选者，但它面临着载体免疫方面的重大问题，并且进入粘膜组织的能力未知。纳米颗粒作为疫苗载体具有一些优势，但面临免疫原性、致癌性和制造质量问题。该提案探讨了使用由自体人类蛋白质组成的生物纳米颗粒（“金库”），装载 HIV-1 序列作为疫苗。穹窿已被证明对 CTL 反应具有免疫原性并可进入粘膜免疫系统。此外，它们由通常存在于细胞质中的自身蛋白组成，因此不具有免疫原性或致癌性，并且易于生产且质量稳定。这两个目标是：目标 1：创建携带保守的 HIV-1 蛋白序列的靶向穹窿；目标 2：确认系统和粘膜免疫区室中穹窿的免疫原性。