RECOMBINANT VEHICLES, PARTICLES AND HSP FUSIONS AS HIV VACCINE

作为 HIV 疫苗的重组载体、颗粒和热休克蛋白融合体

• 批准号: 6234748
• 负责人: RICHARD YOUNG
• 金额: $ 30.72万
• 依托单位: WHITEHEAD INSTITUTE FOR BIOMEDICAL RES
• 依托单位国家: 美国
• 财政年份: 1996
• 资助国家: 美国
• 起止时间: 1996-12-01 至 1998-04-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6234748
• 关键词: AIDS vaccines; Bacillus Calmette Guerin vaccine; Escherichia coli; Mycobacterium bovis; bacterial antigens; bacterial proteins; chimeric proteins; clone cells; fusion gene; human immunodeficiency virus 1; laboratory mouse; live vaccine; lymphokines; microorganism immunology; molecular cloning; mutant; nonhuman therapy evaluation; recombinant DNA; recombinant proteins; simian immunodeficiency virus; stress proteins; virus antigen; virus genetics; virus protein; viruslike particle

This proposal is designed to further develop three types of vaccine candidates: recombinant stress protein fusions, HIV and SIV genome-less particles, and live recombinant BCG vehicles that express antigens and lymphokines. We plan to engineer novel recombinant fusion proteins that incorporate mycobacterial stress proteins and retroviral proteins, exploiting the unusual immunological properties of stress proteins. We will continue to develop genetically inactivated HIV/SIV particles as vaccine candidates by constructing stable cell lines that produce the noninfectious retroviral mutants particles. We will also continue to generate and test the immune response to new forms of recombinant BCG vaccines, especially those that secrete interleukin. We are undertaking the simultaneous development of these three vaccine candidates because we recognize that an efficacious HIV vaccine may require multiple components. Our strategy is to investigate the humoral and cellular immune response to each reagent in mice, to optimize conditions required for eliciting CD8+ CTL, and to provide these data and reagents to investigators in other NCVDG programs and at NIAID for further studies in primates. The stress protein fusions, genetically inactivated retroviral particles, and BCG recombinants will be provided to specific NCVDGs and to NIAID for tests of efficacy in animal models. A vaccine study with BCG-SIV recombinants is already underway in collaboration with the NCVDG under Dr. Murray Gardner. The long-term goals of this research program are to improve our understanding of HIV biology and immunology and to develop an HIV vaccine candidate.

该提案旨在进一步开发三种类型的疫苗 候选者：重组应激蛋白融合、HIV 和 SIV 无基因组 颗粒和表达抗原的活重组卡介苗载体 淋巴因子。 我们计划设计新型重组融合蛋白 结合分枝杆菌应激蛋白和逆转录病毒蛋白， 利用应激蛋白不寻常的免疫学特性。 我们 将继续开发基因灭活的 HIV/SIV 颗粒 通过构建产生候选疫苗的稳定细胞系 非感染性逆转录病毒突变体颗粒。 我们也将继续 生成并测试对新型重组卡介苗的免疫反应 疫苗，尤其是那些分泌白细胞介素的疫苗。 我们正在承担 同时开发这三种候选疫苗是因为 我们认识到，有效的艾滋病毒疫苗可能需要多种方法 成分。 我们的策略是研究体液和细胞 小鼠对每种试剂的免疫反应，以优化所需的条件 用于引发 CD8+ CTL，并提供这些数据和试剂 其他 NCVDG 项目和 NIAID 的研究人员进行进一步研究 在灵长类动物中。 应激蛋白融合体、基因灭活的逆转录病毒颗粒、 BCG 重组体将提供给特定的 NCVDG 和 NIAID 动物模型中的功效测试。 BCG-SIV 疫苗研究 重组已经在与 NCVDG 合作进行 默里·加德纳博士。 该研究计划的长期目标是提高我们的 了解艾滋病毒生物学和免疫学并开发艾滋病毒疫苗 候选人。