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.

该副本是利用众多研究子项目之一 由NIH/NCRR资助的中心赠款提供的资源。子弹和 调查员（PI）可能已经从其他NIH来源获得了主要资金， 因此可以在其他清晰的条目中代表。列出的机构是 对于中心，这不一定是调查员的机构。 该项目的总体目标是确定策略，通过这些策略，可以显着增加基于改良的疫苗Ankara（MVA）基于改良的疫苗（MVA）的艾滋病疫苗的免疫原性。 在这个项目中，我们开发了一种基于MVA的HIV疫苗，从中删除了几种内源性痘病毒免疫避免基因，表达了共识HIV亚型C GAG和ENV抗原。 与父母对照载体相比，该疫苗已显示该疫苗在MHC-透射率群体中，与父母对照载体相比，HIV特异性CD8和CD4 T细胞反应以及HIV包膜特异性抗体反应的水平明显更高。 目前使用该疫苗正在进行的研究包括恒河猕猴中的临床前试验，该试验旨在检验以下假设：这种改善的载体的免疫原性可以通过与特定的Toll样受体（TLR）-7和-9个激动剂共同管理而进一步增强。 此外，在恒河猕猴中评估了表达SIV而不是HIV的类似重组MVA载体，因为它们具有引起全身性和粘膜免疫反应的能力，并在粘膜SIVMAC239挑战中进行了保护，并在同源型免疫方案和伴随毒气中均具有抗粘膜sivmac239挑战。 特别是，鉴于泰国的HIV疫苗疗效试验的最新阳性结果（RV144），从痘病毒载体中开发高度免疫原性的艾滋病疫苗仍然是该领域的高度优先级。