PROPHYLACTIC & THERPEUTIC DNA IMMUNIZATION AGAINST HCV

预防性

• 批准号: 6534245
• 负责人: ALFRED M PRINCE
• 金额: $ 45.8万
• 依托单位: NEW YORK BLOOD CENTER
• 依托单位国家: 美国
• 财政年份: 1999
• 资助国家: 美国
• 起止时间: 1999-09-30 至 2004-06-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6534245
• 关键词: Pan; Poxviridae; active immunization; cellular immunity; chimeric proteins; cross immunity; cytokine; cytotoxic T lymphocyte; hepatitis C; hepatitis C virus; humoral immunity; immunogenetics; neutrophil; plasmids; recombinant DNA; recombinant proteins; vaccine development; vector vaccine

The goals of this study are to evaluate the role of humoral and cellular (CTL) effector mechanisms in natural and induced immunity to HCV, and to achieve broadly cross reactive prophylactic immunization. Immune responses will be determined during the development of self-limited or chronic infections in HCV inoculated chimpanzees to evaluate correlates of immunity. The experiments will also evaluate a variety of HCV genomic constructs in plasmids and canary pox vectors, and E1E2 proteins, for induction of humoral and cellular immune responses in chimpanzees. Lymphokine genes (GM-CSF, IL-2 or IL-12) will be used together with HCV viral genes, to assess their efficacy in enhancement of immune responses. The humoral, CD4 T-helper and CTL responses will be analyzed quantitatively and qualitatively. The immunogenicity of HCV genes presented as fusion proteins with ubiquitin and secreting and non-secreting HCV gene-containing plasmids will be compared.

本研究的目的是评估体液和细胞（CTL）效应机制在自然和诱导的HCV免疫中的作用，并实现广泛的交叉反应性预防性免疫。 将在HCV接种黑猩猩发生自限性或慢性感染期间测定免疫应答，以评价免疫相关性。这些实验还将评估质粒和金丝雀痘载体中的各种HCV基因组构建体以及E1 E2蛋白，用于诱导黑猩猩的体液和细胞免疫应答。 将与HCV病毒基因一起使用巨噬细胞因子基因（GM-CSF、IL-2或IL-12），以评估它们在增强免疫应答方面的功效。 将对体液、CD 4辅助性T细胞和CTL应答进行定量和定性分析。将比较作为与泛素的融合蛋白以及含有分泌型和非分泌型HCV基因的质粒的HCV基因的免疫原性。