SARS病毒S蛋白特異性單克隆抗體制備和抗原識別位點(diǎn)鑒定
發(fā)布時(shí)間:2018-05-17 18:52
本文選題:嚴(yán)重急性呼吸綜合癥 + 嚴(yán)重急性呼吸綜合癥相關(guān)病毒 ; 參考:《第三軍醫(yī)大學(xué)》2005年博士論文
【摘要】: 嚴(yán)重急性呼吸綜合癥(Severe acute respiratory syndrome ,SARS)是一種新型傳染性疾病,其病原體為SARS病毒(S ARS-associated coronavirus ,SARS-CoV)。SARS于2002年年底首先出現(xiàn)在中國廣東省,之后沿著國際航線迅速向全球傳播,在遍及五大洲的33個國家和地區(qū)引起了8,450病例和810人死亡。這次SARS全球爆發(fā)嚴(yán)重威脅了世界公共健康和社會經(jīng)濟(jì)的穩(wěn)定。盡管這次爆發(fā)在2003年最終得到了控制,后來在臺灣、新加坡和中國大陸的實(shí)驗(yàn)室由于意外事故釋放病毒引起了在這些地區(qū)的獨(dú)立的小規(guī)模爆發(fā)。2003年年底至2004年年初,中國廣東報(bào)道了新的感染病例,病人與被SARS病毒感染的動物有過接觸,而這次的病毒毒株與2002-2003期間流行的毒株有明顯不同[1]。這些事件說明SARS在將來隨時(shí)可能會發(fā)生,或者由實(shí)驗(yàn)室保存的樣品引起,或者由動物宿主體內(nèi)的SARS樣病毒進(jìn)化而來的毒株引起。因此,研制SARS檢測診斷制劑、制備有效和安全的疫苗以預(yù)防SARS的流行和為生物防御做準(zhǔn)備是一項(xiàng)目前十分緊迫的任務(wù)。 臨床研究表明,康復(fù)期SARS患者的血清抗體對治療危重的SARS患者有一定的療效。因此,研制抗SARS-CoV的抗體對于探索SARS的特異性治療具有重要意義。雖然在SARS肆虐之際,鼠源性單克隆抗體并不能解燃眉之急,但是從SARS其他相關(guān)研究和建立免疫學(xué)診斷方法角度來看,單克隆抗體的研制卻是必不可缺的。實(shí)驗(yàn)室早期診斷是控制疾病的重要手段。以RT-PCR為基礎(chǔ)的病毒核酸檢測法存在敏感性和特異性的問題,測定病毒特異抗體的血清學(xué)方法不能在SARS發(fā)病的早期提供診斷結(jié)果。建立基于SARS病毒特異單克隆抗體的SARS病毒抗原檢測方法,對SARS的早期診斷可能會有重要作用。 滅活SARS病毒由于其容易制備的特點(diǎn)可能會成為可用于臨床的第一代疫苗,但它的安全性是一個很大的問題。生產(chǎn)疫苗的工人在處理濃縮的活病毒時(shí)有被感染的危險(xiǎn),未被完全滅活的病毒可以在接種人群中引起SARS的爆發(fā),而且有些病毒蛋白可能會引起有害的免疫反應(yīng)或炎癥反應(yīng),甚至導(dǎo)致SARS樣疾病。在SARS病毒的結(jié)構(gòu)蛋白中S蛋白是最大和最復(fù)雜的結(jié)構(gòu)蛋白,屬于I型跨膜糖蛋白,負(fù)責(zé)病毒與靶細(xì)胞的結(jié)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.
【學(xué)位授予單位】:第三軍醫(yī)大學(xué)
【學(xué)位級別】:博士
【學(xué)位授予年份】:2005
【分類號】:R392
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