IMMUNOPATHOGENESIS OF RUBELLA VIRUS ASSOCIATED AUTOIMMUNE DYSFUNCTION

风疹自然感染或减毒免疫的并发症 25%的成年女性接种风疹疫苗，包括暂时性和慢性 关节炎。了解导致生活并发症的事件 轮状病毒疫苗可能会导致未来轮状病毒疫苗的改进。至 了解轮状病毒相关病理的机制，我们正在分析 病毒RNA的基本成分及其各自的功能 在病毒复制过程中与宿主和病毒成分的相互作用。我们 已经确定了两种宿主编码的蛋白质La和Calreticrin，它们是 已知的自身抗原，是轮状病毒复制所必需的。参与其中 自身抗原在RV发病机制中的作用具有临床意义，因为 自身抗原抗体是自身免疫性疾病中常见的疾病。我们 发现干燥综合征和系统性红斑狼疮患者的血清 红斑狼疮患者有针对RV自身抗原复合体的抗体。这个 自身免疫患者对轮状病毒自身抗原复合体的抗体应答 提示RV相关性关节病可能存在类似的机制。 该项目直接涉及活病毒疫苗的安全问题。 总体而言，特别是轮状病毒疫苗。使用房车进行的研究 将作为了解疫苗相关不良反应的指南 与轮状病毒疫苗相关的急性或慢性关节炎等反应。它 也为未来病毒疫苗的设计提供了洞察力，必须 没有不良影响。此外，我们还开发了内部技术诀窍 现代技术在重组病毒疫苗研制中的应用 目前正在由这些公司开发。因此，使该机构能够 在此类问题上为制造商提供指导。房车的结局 研究也对分析方法的发展产生了额外的影响 对评价生物制品纯度有用的方法学 在制造过程和批次放行测试期间。获得的知识 通过对房车的研究，可以为房车的发展提供动力 评估活病毒制造过程的监管政策 疫苗以及效率较低的重组疫苗 太麻烦了。

Complications of natural rubella infection or immunization with attenuated rubella vaccine in 25% of adult women include transient and chronic arthritis. Understanding the events leading to complications due to live RV vaccine would potentially lead to improvement in future RV vaccines. To understand the mechanisms of RV -associated pathology, we are analyzing the function of both the essential elements of virus RNA and their interaction with host and viral components during viral replication. We have identified two host-encoded proteins La and calreticulin,that are known autoantigens and are essential for RV replication. The involvement of autoantigens in RV pathogenesis is of clinical interest, because antibodies to autoantigens is common occurance in autoimmune diseases. We have found that sera from patients with Sjorgens syndrome and Systemic Lupus Erythrematous have antibodies against RV-autoantigen complexes. The antibody response to RV-autoantigen complexes in autoimmune patients suggests that similar mechanism may occur in RV-associated arthropathy. The project deals directly with the safety issues of live- viral vaccines in general and of RV vaccine in particular. Research conducted with RV will serve as a guideline for understanding the vaccine related adverse reactions such as RV vaccine-associated acute or chronic arthritis. It also provides insight in the design of future viral vaccines that must be free of adverse effects. Further, we have developed in-house know-how of modern techniques used in development of recombinant viral vaccines currently being developed by the companies. Thus, enabling the agency to provide guidance to the manufacturers in such issues. Outcome of RV research has also an added impact on the development of assays and methodologies which are useful in evaluating the purity of biologics during manufacturing process and lot release testing. Knowledge gained from the research done with RV can provide impetus in the development of regulatory policy to evaluate manufacturing process for live-viral vaccines as well as recombinant vaccines that isefficient and less cumbersome.