Development of needle-free, vectorless, RNA-based vaccines for HIV

开发无针、无载体、基于 RNA 的 HIV 疫苗

基本信息

批准号：
7896609
负责人：
DANIEL Garrett KAVANAGH
金额：
$ 25.45万
依托单位：
MASSACHUSETTS GENERAL HOSPITAL
依托单位国家：
美国
项目类别：
财政年份：
2009
资助国家：
美国
起止时间：
2009-07-20 至 2012-06-30
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/7896609
关键词：
Address Adenovirus Vector Adjuvant Agonist Animal Model Antigen-Presenting Cells Antigens Antiviral Agents Autologous Cancer Patient Characteristics Clinical Clinical Trials Cytoplasm Data Dendritic Cells Development Dose Drug Formulations Electroporation Eye Gagging Goals HIV HIV Antigens HIV Infections HIV vaccine Immune Immune response Immune system Immunity Immunotherapy In Vitro Infusion procedures Injection of therapeutic agent Interleukin-10 Intranasal Administration Investigation Ligands Light Liver Macaca mulatta Measures Mediating Messenger RNA Methods Modeling Mucosal Immunity Mus Needles Nucleic Acids Peripheral Blood Mononuclear Cell Phenotype Predisposition Primates Protein Biosynthesis Public Health RNA Recombinant Proteins Recombinants Reporting Respiratory System Respiratory tract structure Rodent Route Schedule Severities Site System T cell response T-Lymphocyte Technology Therapeutic Uses Transfection Vaccinated Vaccination Vaccines Viral Vector Virus Diseases base cell type cytokine flexibility immune activation immunogenic immunogenicity in vivo influenza virus vaccine interest nanoparticle new technology prevent prophylactic public health relevance success synthetic construct vaccine delivery vaccine development vaccine efficacy vaccinology vector

项目摘要

DESCRIPTION (provided by applicant): In order to develop an effective vaccine against HIV, it will be necessary to develop new methods to prime T cell responses against HIV antigens. One way to prime such T cell responses is to create recombinant viral vectors that express HIV antigens. Recent results from a large scale clinical trial using recombinant adenovirus vectors as an experimental prophylactic HIV vaccine raise significant concerns that immune responses directed against the viral vector may have had a detrimental effect on vaccine efficacy, or may even have increased susceptibility to HIV infection. The purpose of the project described in this application is to develop new methods to prime HIV-specific T cell responses in a "vectorless" manner. Our proposed method will use various new nanoparticle technologies permit vaccine delivery by an intranasal route. PUBLIC HEALTH RELEVANCE: The goal of this project is to develop a vaccine that can prevent or reduce the severity of HIV infection in vaccinated subjects. The proposed vaccine will be composed of nucleic acids (RNA) and closely related compounds and will be administered by an intranasal route. If successful this vaccine will prime protective immunity in the absence of viral vectors or recombinant proteins, and without requiring needles or injection for delivery.

描述（由申请人提供）：为了开发针对艾滋病毒的有效疫苗，有必要开发新方法来针对HIV抗原的T细胞反应。这种T细胞反应的一种基本方法是创建表达HIV抗原的重组病毒载体。一项大规模临床试验的最新结果使用重组腺病毒载体作为实验性的预防性HIV疫苗引起了严重的关注，即针对病毒载体的免疫反应可能对疫苗疗效产生有害作用，甚至可能对HIV感染的易感性提高。本应用程序中描述的项目的目的是开发新方法，以“无矢量”方式为HIV特异性T细胞响应素。我们提出的方法将使用各种新的纳米颗粒技术允许通过鼻内途径输送疫苗。公共卫生相关性：该项目的目标是开发一种可以预防或减少接种疫苗受试者中艾滋病毒感染严重性的疫苗。拟议的疫苗将由核酸（RNA）组成，并与密切相关的化合物组成，并将通过鼻内途径施用。如果成功，该疫苗将在没有病毒载体或重组蛋白的情况下进行保护性免疫，而无需针头或注射以进行输送。