PROPHYLACTIC & THERPEUTIC DNA IMMUNIZATION AGAINST HCV

本研究的目的是评估体液和细胞(CTL)效应机制在丙型肝炎病毒自然免疫和诱导免疫中的作用，并实现广泛的交叉反应预防性免疫。在接种丙型肝炎病毒的黑猩猩发生自限性或慢性感染的过程中，将测定免疫反应，以评估免疫相关因素。这些实验还将评估在质粒和金丝雀痘载体中的各种丙型肝炎病毒基因组结构，以及E1E2蛋白，以诱导黑猩猩的体液和细胞免疫反应。淋巴因子基因(GM-CSF、IL-2或IL-12)将与丙型肝炎病毒基因一起使用，以评估它们在增强免疫反应方面的效果。体液、CD4T辅助细胞和CTL反应将进行定量和定性的分析。比较以融合蛋白与泛素和分泌型和非分泌型丙型肝炎病毒基因为载体的丙型肝炎病毒基因的免疫原性。

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.