SARS病毒S蛋白特异性单克隆抗体制备和抗原识别位点鉴定

发布时间：2018-05-17 18:52

本文选题：严重急性呼吸综合症 + 严重急性呼吸综合症相关病毒　；参考：《第三军医大学》2005年博士论文

【摘要】： 严重急性呼吸综合症(Severe acute respiratory syndrome ,SARS)是一种新型传染性疾病,其病原体为SARS病毒(S ARS-associated coronavirus ,SARS-CoV)。SARS于2002年年底首先出现在中国广东省,之后沿着国际航线迅速向全球传播,在遍及五大洲的33个国家和地区引起了8,450病例和810人死亡。这次SARS全球爆发严重威胁了世界公共健康和社会经济的稳定。尽管这次爆发在2003年最终得到了控制,后来在台湾、新加坡和中国大陆的实验室由于意外事故释放病毒引起了在这些地区的独立的小规模爆发。2003年年底至2004年年初,中国广东报道了新的感染病例,病人与被SARS病毒感染的动物有过接触,而这次的病毒毒株与2002-2003期间流行的毒株有明显不同[1]。这些事件说明SARS在将来随时可能会发生,或者由实验室保存的样品引起,或者由动物宿主体内的SARS样病毒进化而来的毒株引起。因此,研制SARS检测诊断制剂、制备有效和安全的疫苗以预防SARS的流行和为生物防御做准备是一项目前十分紧迫的任务。临床研究表明,康复期SARS患者的血清抗体对治疗危重的SARS患者有一定的疗效。因此,研制抗SARS-CoV的抗体对于探索SARS的特异性治疗具有重要意义。虽然在SARS肆虐之际,鼠源性单克隆抗体并不能解燃眉之急,但是从SARS其他相关研究和建立免疫学诊断方法角度来看,单克隆抗体的研制却是必不可缺的。实验室早期诊断是控制疾病的重要手段。以RT-PCR为基础的病毒核酸检测法存在敏感性和特异性的问题,测定病毒特异抗体的血清学方法不能在SARS发病的早期提供诊断结果。建立基于SARS病毒特异单克隆抗体的SARS病毒抗原检测方法,对SARS的早期诊断可能会有重要作用。灭活SARS病毒由于其容易制备的特点可能会成为可用于临床的第一代疫苗,但它的安全性是一个很大的问题。生产疫苗的工人在处理浓缩的活病毒时有被感染的危险,未被完全灭活的病毒可以在接种人群中引起SARS的爆发,而且有些病毒蛋白可能会引起有害的免疫反应或炎症反应,甚至导致SARS样疾病。在SARS病毒的结构蛋白中S蛋白是最大和最复杂的结构蛋白,属于I型跨膜糖蛋白,负责病毒与靶细胞的结合、
[Abstract]:Severe Acute Respiratory Syndrome (SARS) is a new type of infectious disease. Its pathogen is SARS virus, S ARS-associated coronavirus, SARS-CoV. SARS first appeared in Guangdong Province of China at the end of 2002, and then spread rapidly to the world along international routes. 8450 cases and 810 deaths occurred in 33 countries and territories across five continents. The global outbreak of SARS has seriously threatened the world's public health and social and economic stability. Although the outbreak was finally brought under control in 2003, laboratories in Taiwan, Singapore and mainland China have since caused small, independent outbreaks in these areas due to accidental release of the virus. New cases of infection have been reported in Guangdong, China. The patient has been in contact with animals infected with the SARS virus, and the virus strain this time is significantly different from that prevalent during 2002-2003 [1]. These events suggest that SARS may occur at any time in the future, either by laboratory samples or by strains of SARS like viruses in animal hosts. Therefore, it is an urgent task to develop SARS diagnostic agents, to prepare effective and safe vaccines to prevent the spread of SARS and to prepare for biological defense. Clinical studies have shown that serum antibodies of convalescent SARS patients are effective in the treatment of critical SARS patients. Therefore, the development of anti-SARS-CoV antibody is of great significance for exploring the specific treatment of SARS. Although murine monoclonal antibody can not solve the urgent problem at the time of SARS, the development of monoclonal antibody is indispensable from the point of view of other related research of SARS and establishment of immunological diagnosis method. Early laboratory diagnosis is an important means of disease control. The virus nucleic acid detection based on RT-PCR has the problem of sensitivity and specificity. The serological method for the detection of virus specific antibody can not provide diagnostic results in the early stage of the onset of SARS. The detection method of SARS virus antigen based on SARS virus specific monoclonal antibody may play an important role in the early diagnosis of SARS. Inactivated SARS virus may become the first generation vaccine for clinical use because of its easy preparation, but its safety is a big problem. Vaccine-producing workers are at risk of being infected when dealing with concentrated live viruses, viruses that are not completely inactivated can cause SARS outbreaks in vaccinated populations, and some viral proteins may cause harmful immune or inflammatory reactions. It even causes SARS-like disease. Among the structural proteins of SARS virus, S protein is the largest and most complex structural protein, which belongs to type I transmembrane glycoprotein and is responsible for the binding of the virus to target cells.
【学位授予单位】：第三军医大学
【学位级别】：博士
【学位授予年份】：2005
【分类号】：R392

【同被引文献】