THERAPEUTIC DNA/MVA VACCINES FOR HIV/AIDS

HIV/艾滋病治疗性 DNA/MVA 疫苗

• 批准号: 8357462
• 负责人: Rama Rao Amara
• 金额: $ 5.95万
• 依托单位: EMORY UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2011
• 资助国家: 美国
• 起止时间: 2011-08-01 至 2012-04-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8357462
• 关键词: AIDS/HIV problem; Acquired Immunodeficiency Syndrome; Anti-Retroviral Agents; CD4 Positive T Lymphocytes; CD8B1 gene; DNA; DNA/MVA vaccine; Funding; Gagging; Grant; HIV Vaccine Trials Network; HIV vaccine; Immune system; Infection; Macaca; Modeling; Mutation; National Center for Research Resources; Phase; Pilot Projects; Primates; Principal Investigator; Prior Therapy; Research; Research Infrastructure; Resources; SIV; SIV Vaccines; Source; T cell response; T-Lymphocyte; T-Lymphocyte Epitopes; Testing; Therapeutic; Time; United States National Institutes of Health; Vaccination; Viral; Virus; cost; exhaustion; healthy volunteer; immunogenicity; neutralizing antibody; prototype

This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. Primary support for the subproject and the subproject's principal investigator may have been provided by other sources, including other NIH sources. The Total Cost listed for the subproject likely represents the estimated amount of Center infrastructure utilized by the subproject, not direct funding provided by the NCRR grant to the subproject or subproject staff. We are currently testing the therapeutic potential of a DNA/MVA SIV vaccine in macaques infected with SIV251 in combination with anti-retroviral therapy (ART). This DNA/MVA SIV vaccine is a prototype of HIV vaccine that is currently being tested in healthy volunteers for immunogenicity (Phase 2a) through HVTN/Geovax Inc. Two pilot studies, TH-12 and TH-32, have been completed. TH-12 tested whether therapeutic vaccination had the potential to be effective in macaques placed on ART soon after infection (12 weeks); and TH-32 tested for therapeutic potential late after infection when the group is developing AIDS (32 weeks). TH-18 is currently testing an intermediate time, 18 weeks post infection. SIV infections are a good model for therapeutic HIV vaccines because over the course of pathogenic SIV infections there is a progressive loss of viral control due to the destruction of CD4 T cells, CD8 T cell exhaustion, and the selection of viral mutations that allow CD8 T cell and neutralizing antibody escape. The results of the pilot studies suggest the following important findings: (1) Vaccinations combined with ART elicit highly functional CD8 and CD4 T cells irrespective of either early (12-18 weeks) or late (32 weeks) ART initiation. (2) However, vaccinations combined with early ART (prior to substantial viral escape and immune system destruction) are more effective than vaccinations combined with late ART. (3) The breadth of the elicited CD8 T cell epitopes for Gag and their match to the CD8 T cell response stimulated by the re-emergent virus is important for control.

这个子项目是许多利用资源的研究子项目之一 由NIH/NCRR资助的中心拨款提供。子项目的主要支持 而子项目的主要调查员可能是由其他来源提供的， 包括其它NIH来源。 列出的子项目总成本可能 代表子项目使用的中心基础设施的估计数量， 而不是由NCRR赠款提供给子项目或子项目工作人员的直接资金。 我们目前正在测试DNA/MVA SIV疫苗与抗逆转录病毒疗法（ART）联合在感染SIV 251的猕猴中的治疗潜力。这种DNA/MVA SIV疫苗是HIV疫苗的原型，目前正在通过HVTN/Geovax Inc.在健康志愿者中进行免疫原性测试（2a期）。已经完成了两项试点研究，即TH-12和TH-32。TH-12测试了治疗性疫苗接种是否有可能在感染后不久（12周）接受ART的猕猴中有效; TH-32测试了感染后晚期（32周）发生AIDS时的治疗潜力。TH-18目前正在测试一个中间时间，感染后18周。SIV感染是治疗性HIV疫苗的良好模型，因为在致病性SIV感染的过程中，由于CD 4 T细胞的破坏、CD 8 T细胞的耗尽以及允许CD 8 T细胞和中和抗体逃逸的病毒突变的选择，存在病毒控制的进行性丧失。初步研究的结果表明了以下重要发现：（1）疫苗接种与ART联合诱导高功能的CD 8和CD 4 T细胞，无论早期（12-18周）还是晚期（32周）ART启动。(2)然而，疫苗接种与早期ART（在病毒大量逃逸和免疫系统破坏之前）相结合比疫苗接种与晚期ART相结合更有效。（3）引发的Gag CD 8 T细胞表位的宽度及其与CD 8 T细胞的匹配由重新出现的病毒刺激的细胞反应对于控制很重要。