OPTIMIZE THE IMMUNOGENICITY OF MVA-BASED AIDS VACCINES

优化基于 MVA 的艾滋病疫苗的免疫原性

• 批准号: 8172361
• 负责人: DAVID A GARBER
• 金额: $ 5.48万
• 依托单位: EMORY UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2010
• 资助国家: 美国
• 起止时间: 2010-05-01 至 2011-04-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8172361
• 关键词: AIDS Vaccines; Acquired Immunodeficiency Syndrome; Adenovirus Vector; Agonist; Antibody Formation; CD4 Positive T Lymphocytes; CD8B1 gene; Computer Retrieval of Information on Scientific Projects Database; Consensus; Development; Funding; Gagging; Genes; Goals; Grant; HIV; HIV Antigens; HIV vaccine; Immune; Immunization; Institution; Light; Macaca mulatta; Modified Vaccinia Virus Ankara; Mucosal Immune Responses; Population; Poxviridae; Recombinants; Regimen; Research; Research Personnel; Resources; SIV; Source; T cell response; Testing; Thailand; United States National Institutes of Health; Vaccines; Viral Vector; base; design; efficacy trial; env Gene Products; human TLR7 protein; immunogenic; immunogenicity; improved; poxvirus vectors; preclinical study; vaccine efficacy; vector; vector control

This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. The subproject and investigator (PI) may have received primary funding from another NIH source, and thus could be represented in other CRISP entries. The institution listed is for the Center, which is not necessarily the institution for the investigator. The overall goal of this project is to identify strategies by which the immunogenicity of AIDS vaccines that are derived from Modified Vaccinia Ankara (MVA)-based viral vectors can be significantly augmented. In this project, we have developed and characterized an MVA-based HIV vaccine, from which several endogenous poxvirus immune-evasion genes have been deleted, that expresses consensus HIV subtype C Gag and Env antigens. This vaccine has been shown to elicit significantly higher levels of HIV-specific CD8 and CD4 T cell responses, as well as HIV envelope-specific antibody responses, as compared to the parental control vector, in MHC-disparate populations of rhesus macaques. Presently ongoing studies with this vaccine include a preclinical trial in rhesus macaques that is designed to test the hypothesis that the immunogenicity of this improved vector may be even further augmented through co-administration with specific toll-like receptor (TLR) -7, and -9 agonists. In addition, analogous recombinant MVA vectors expressing SIV, rather than HIV, antigens are currently being assessed in rhesus macaques for their ability to elicit systemic and mucosal immune responses, as well as protection against mucosal SIVmac239 challenge, following both homologous prime-boost immunization regimens and heterologous prime-boost immunizations with adenoviral vectors. Particularly, in light of recent positive results from the HIV vaccine efficacy trial in Thailand (RV144), the development of highly immunogenic AIDS vaccines from poxvirus vectors remains a high priority for the field.

这个子项目是许多研究子项目中利用 资源由NIH/NCRR资助的中心拨款提供。子项目和 调查员(PI)可能从NIH的另一个来源获得了主要资金， 并因此可以在其他清晰的条目中表示。列出的机构是 该中心不一定是调查人员的机构。 该项目的总体目标是确定可以显著增强基于改良安卡拉牛痘(MVA)病毒载体的艾滋病疫苗免疫原性的策略。在这个项目中，我们开发并鉴定了一种基于MVA的HIV疫苗，其中的几个内源性痘病毒免疫逃避基因已经被删除，表达了一致的HIV C亚型Gag和Env抗原。 与亲本对照载体相比，该疫苗已被证明在MHC不同的猕猴种群中诱导出显著更高水平的HIV特异性CD8和CD4T细胞反应，以及HIV包膜特异性抗体反应。 目前正在进行的这种疫苗的研究包括在恒河猴身上进行的临床前试验，旨在测试这样一种假设，即通过与特定的Toll样受体(TLR)-7和-9激动剂共同接种，这种改进的载体的免疫原性可能会进一步增强。 此外，表达SIV而不是HIV抗原的类似重组MVA载体目前正在恒河猴身上进行评估，以评估它们诱导系统和粘膜免疫反应的能力，以及对黏膜SIVmac239攻击的保护作用，包括同源Prime-Boost免疫方案和异源Prime-Boost用腺病毒载体免疫。 特别是，鉴于最近泰国艾滋病毒疫苗功效试验(RV144)的阳性结果，从痘病毒载体开发高免疫原性艾滋病疫苗仍然是该领域的高度优先事项。