IMMUNOPATHOGENESIS OF RUBELLA VIRUS ASSOCIATED AUTOIMMUNE DYSFUNCTION

自然风疹感染或接种减毒风疹疫苗的并发症 25%的成年妇女接种风疹疫苗，包括短暂性和慢性风疹。 关节炎了解导致肝移植并发症的事件 RV疫苗可能会导致未来RV疫苗的改进。到 了解RV相关病理的机制，我们正在分析 病毒RNA的基本元件及其 在病毒复制过程中与宿主和病毒成分相互作用。我们 已经鉴定出两种宿主编码的蛋白质La和钙网蛋白， 已知的自身抗原和RV复制所必需的。参与 RV发病机制中的自身抗原是临床感兴趣的，因为 自身抗原抗体是自身免疫性疾病中常见的抗体。我们 已经发现，来自Sjorgens综合征和全身性 红斑狼疮具有抗RV-自身抗原复合物的抗体。的 自身免疫患者对RV-自身抗原复合物的抗体应答 提示在RV相关性关节病中可能发生类似机制。 该项目直接涉及活病毒疫苗的安全问题 尤其是RV疫苗。使用RV进行的研究 将作为了解疫苗相关不良反应的指南 反应，如RV疫苗相关的急性或慢性关节炎。它 还为未来病毒疫苗的设计提供了见解， 无不良影响。 此外，我们还开发了内部专有技术， 用于开发重组病毒疫苗的现代技术 目前，公司正在开发。 因此，使该机构能够 在这些问题上为制造商提供指导。RV结局 研究还对分析的发展产生了额外的影响， 用于评价生物制品纯度的方法 在生产工艺和批放行检测期间。获得的知识 从RV所做的研究可以提供动力的发展， 评估活病毒疫苗生产工艺的监管政策 疫苗以及重组疫苗， 繁琐.

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.