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的一个 由NIH/NCRR资助的中心赠款提供的资源。子项目和 研究者（PI）可能从另一个NIH来源获得了主要资金， 因此可以在其他CRISP条目中表示。所列机构为 研究中心，而研究中心不一定是研究者所在的机构。 该项目的总体目标是确定策略，通过该策略，可以显着增强来自基于改良安卡拉牛痘（MVA）的病毒载体的艾滋病疫苗的免疫原性。 在这个项目中，我们已经开发并表征了基于MVA的HIV疫苗，其中几个内源性痘病毒免疫逃避基因已被删除，表达共识HIV亚型C Gag和Env抗原。 与亲本对照载体相比，该疫苗已显示在MHC不同的恒河猴群体中引起显著更高水平的HIV特异性CD 8和CD 4 T细胞应答以及HIV特异性抗体应答。 目前正在进行的关于该疫苗的研究包括在恒河猴中进行的临床前试验，该临床前试验被设计用于测试以下假设：该改进的载体的免疫原性可以通过与特异性toll样受体（TLR）-7和-9激动剂共同施用而进一步增强。 此外，目前正在恒河猴中评估表达SIV而非HIV抗原的类似重组MVA载体在同源初免-加强免疫方案和用腺病毒载体进行异源初免-加强免疫后引发全身和粘膜免疫应答以及针对粘膜SIVmac 239攻击的保护的能力。 特别是，鉴于最近在泰国进行的HIV疫苗功效试验（RV 144）取得了积极的结果，利用痘病毒载体开发高免疫原性的艾滋病疫苗仍然是该领域的高度优先事项。