DNA/MVA IMMUNOGENS, CROSS-CLADE RESPONSES

DNA/MVA 免疫原，跨进化枝反应

• 批准号: 7715685
• 负责人: HARRIET L ROBINSON
• 金额: $ 8.16万
• 依托单位: EMORY UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2008
• 资助国家: 美国
• 起止时间: 2008-05-01 至 2009-04-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7715685
• 关键词: Antigens; Binding; CD4 Positive T Lymphocytes; CD8B1 gene; Computer Retrieval of Information on Scientific Projects Database; DNA; Dose; Funding; Gagging; Grant; HIV; HIV vaccine; Human; Immunization; Institution; Intramuscular; Personal Satisfaction; Phase; Placebos; Proteins; Recombinant DNA; Recombinants; Research; Research Personnel; Resources; Saline; Source; T-Lymphocyte; United States National Institutes of Health; Vaccines; Virus-like particle; doxorubicin/mitomycin/vinblastine protocol; env Gene Products; immunogenic; pol genes; programs; response

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. Both the DNA and MVA express Virus Like Particles. A low dose group (n=10) received 0.3 mg JS7 DNA at months 0 and 2, and 107 TCID50 of MVA62 at months 4 and 6. A high dose group (n=30) received 3 mg of JS7 DNA and 108 TCID50 of MVA62 at the same intervals. Placebos received saline (n=8). All inoculations were intramuscular. Both the low and high doses of the vaccine have been well tolerated and immunogenic in humans. Following the 2nd MVA immunization, 77% (20/26) of the high dose, 87% (7/8) of the low dose and none (0/8) of the placebo recipients had responding CD4 T cells; and 42% (11/26) of the high dose, 33% (3/9) of the low dose, and none (0/8) of the placebos had responding CD8 T cells. Responses were targeted to Gag~EnvPol. In contrast to the T cell responses, Ab responses increased with vaccine dose. Following the 2nd MVA inoculation, 88% of the high dose, but only 22%, of the low dose group had anti-Env binding Ab. The 2nd MVA increased the CD8 and Ab responses but not the CD4 responses.

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 中心，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。 DNA 和 MVA 均表达病毒样颗粒。低剂量组 (n=10) 在第 0 个月和第 2 个月接受 0.3 mg JS7 DNA，并在第 4 个月和第 6 个月接受 107 TCID50 的 MVA62。高剂量组 (n=30) 接受 3 mg JS7 DNA 和 108 TCID50 的 MVA62。 MVA62 以相同的间隔。安慰剂接受生理盐水（n=8）。所有接种均为肌内接种。低剂量和高剂量的疫苗在人类中均具有良好的耐受性和免疫原性。第 2 次 MVA 免疫接种后，77% (20/26) 的高剂量组、87% (7/8) 的低剂量组和安慰剂接受者中没有 (0/8) 有响应的 CD4 T 细胞；高剂量组中 42% (11/26)、低剂量组中 33% (3/9) 以及安慰剂组中没有 (0/8) 有响应的 CD8 T 细胞。响应针对 Gag~EnvPol。与 T 细胞反应相反，抗体反应随着疫苗剂量的增加而增加。第 2 次 MVA 接种后，88% 的高剂量组（低剂量组中只有 22%）具有抗 Env 结合抗体。第 2 次 MVA 增加了 CD8 和 Ab 反应，但没有增加 CD4 反应。