DNA/MVA IMMUNOGENS, CROSS-CLADE RESPONSES

DNA/MVA 免疫原，跨进化枝反应

• 批准号: 7562528
• 负责人: HARRIET L ROBINSON
• 金额: $ 10.47万
• 依托单位: EMORY UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2007
• 资助国家: 美国
• 起止时间: 2007-05-01 至 2008-04-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7562528
• 关键词: AIDS/HIV problem; Adjuvant; Affect; Antigens; Avidity; Biological Assay; CD4 Positive T Lymphocytes; CD8B1 gene; Computer Retrieval of Information on Scientific Projects Database; DNA; DNA/MVA vaccine; Dose; Funding; Gagging; Grant; Granulocyte-Macrophage Colony-Stimulating Factor; HIV; HIV vaccine; Height; Human; Immune response; Individual; Institution; Interleukin-2; Mus; Pharmaceutical Preparations; Phase; Phase I Clinical Trials; Production; Proteins; Recombinant DNA; Recombinants; Research; Research Personnel; Resources; Safety; Source; T-Lymphocyte; Testing; United States National Institutes of Health; Vaccines; Viral; Work; doxorubicin/mitomycin/vinblastine protocol; env Gene Products; pol genes; programs; response; volunteer

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. This Program project has resulted in the taking of an HIV/AIDS vaccine into early phase human trials through the HIV Vaccine Trials Network (HVTN). The vaccine consists of priming with a recombinant DNA expressing HIV Gag, Pol, and Env proteins and then boosting with a recombinant MVA expressing the same proteins. The results of HVTN trial 45 (HVTN-045) showed the DNA component of the vaccine to be safe in humans. A 2nd phase 1 trial, HVTN-065 has now been initiated combining the DNA and MVA components of the vaccine. The low dose group (1/10th dose) was initiated in April 2006 and the full dose group in September of 2006. Both of these trials are still in progress. Both are showing the anticipated good safety for DNA/MVA. Ancillary assays being conducted under this Program Project suggest the elicitation of T cell responses in the majority of the low dose volunteers. Other studies supported by the project worked to characterize T cell responses in individuals infected with HIV/AIDS. These showed a deficit in IL-2 production in anti-HIV/AIDS CD8 and CD4 T cells in infected humans. This deficit was partially recovered during anti-viral drug treatment. Other studies also worked on the use of GM-CSF as an adjuvant for the DNA/MVA vaccine. GM-CSF was found to enhance the avidity maturation of the anti-Env Ab response. And finally, studies in mice tested how dose of the MVA immunogen affected immune responses and found that dose had a very limited effect on the height of the immune response.

该子项目是利用该技术的众多研究子项目之一 资源由 NIH/NCRR 资助的中心拨款提供。子项目和 研究者 (PI) 可能已从 NIH 的另一个来源获得主要资金， 因此可以在其他 CRISP 条目中表示。列出的机构是 对于中心来说，它不一定是研究者的机构。 该计划项目已通过艾滋病毒疫苗试验网络（HVTN）将艾滋病毒/艾滋病疫苗纳入早期人体试验。 该疫苗包括用表达 HIV Gag、Pol 和 Env 蛋白的重组 DNA 引发，然后用表达相同蛋白的重组 MVA 加强。 HVTN 试验 45 (HVTN-045) 的结果表明，疫苗的 DNA 成分对人类是安全的。 第二阶段 1 试验 HVTN-065 现已启动，该试验结合了疫苗的 DNA 和 MVA 成分。 低剂量组（1/10剂量）于2006年4月开始，全剂量组于2006年9月开始。这两项试验仍在进行中。 两者均显示出预期的 DNA/MVA 良好安全性。 该计划项目下进行的辅助测定表明，大多数低剂量志愿者都引发了 T 细胞反应。 该项目支持的其他研究致力于表征艾滋病毒/艾滋病感染者的 T 细胞反应。 这些结果表明，感染人类的​​抗 HIV/AIDS CD8 和 CD4 T 细胞中 IL-2 的产生存在缺陷。 这种缺陷在抗病毒药物治疗期间得到了部分恢复。其他研究还致力于使用 GM-CSF 作为 DNA/MVA 疫苗的佐剂。 发现 GM-CSF 可以增强抗 Env Ab 反应的亲和力成熟。 最后，对小鼠的研究测试了 MVA 免疫原的剂量如何影响免疫反应，发现剂量对免疫反应强度的影响非常有限。