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

开发无针、无载体、基于 RNA 的 HIV 疫苗

• 批准号: 7755138
• 负责人: DANIEL Garrett KAVANAGH
• 金额: $ 21.56万
• 依托单位: MASSACHUSETTS GENERAL HOSPITAL
• 依托单位国家: 美国
• 财政年份: 2009
• 资助国家: 美国
• 起止时间: 2009-07-20 至 2011-06-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7755138
• 关键词: Address; Adenovirus Vector; Adjuvant; Agonist; Animal Model; Antigen-Presenting Cells; Antigens; Antiviral Agents; Autologous; Cancer Patient; Characteristics; Classification; Clinical; Clinical Trials; Cytokine Activation; 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-Lymphocyte; Technology; Therapeutic Uses; Transfection; Vaccinated; Vaccination; Vaccines; Viral Vector; Virus Diseases; base; cell type; cytokine; flexibility; immunogenic; immunogenicity; in vivo; influenza virus vaccine; interest; nanoparticle; new technology; prevent; prophylactic; public health relevance; response; success; synthetic construct; vaccine delivery; vaccine development; vaccine efficacy; vaccinology; vector

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HIV的有效疫苗，有必要开发新的方法来引发针对HIV抗原的T细胞应答。引发这种T细胞反应的一种方法是创建表达HIV抗原的重组病毒载体。使用重组腺病毒载体作为实验性预防性HIV疫苗的大规模临床试验的最新结果引起了人们的严重关注，即针对病毒载体的免疫应答可能对疫苗功效具有有害影响，或者甚至可能增加对HIV感染的易感性。本申请中描述的项目的目的是开发以“无载体”方式引发HIV特异性T细胞应答的新方法。我们提出的方法将使用各种新的纳米颗粒技术，允许通过鼻内途径递送疫苗。公共卫生相关性：该项目的目标是开发一种疫苗，可以预防或减少接种疫苗的受试者感染艾滋病毒的严重程度。拟定疫苗将由核酸（RNA）和密切相关的化合物组成，并将通过鼻内途径给药。如果成功，这种疫苗将在没有病毒载体或重组蛋白的情况下引发保护性免疫，并且不需要针头或注射来递送。