發(fā)布時間：2018-06-16 19:44

  本文選題：流感 + 多表位��； 參考：《吉林大學》2010年博士論文

【摘要】： 流感是一種由流感病毒引發(fā)的傳染病,患者以發(fā)熱、粘膜充血、急性呼吸道癥狀為主。該病發(fā)病率高,破壞性強,從二十世紀三十年代人類發(fā)明流感疫苗至今,每年仍有25～50萬人死于流感。季節(jié)性流感以H1、H3亞型為主,而禽流感H5、H7亞型也不斷出現(xiàn)人類感染病例。流感病毒不斷變異,隨時都有可能進化成為大流行流感毒株,世界上很多國家都在研發(fā)新型流感疫苗以應對多種亞型流感大流行。 本研究利用生物信息學方法、免疫學知識,對H1、H3亞型流感病毒的T、B細胞表位進行預測與篩選,獲得CTL表位3條:H1HA545-553、H3HA546-554、H3NP189-197,B和Th細胞表位4條:H1HA142~156、H1HA212~226、H3HA247~261、H3HA287~301。 結合已發(fā)表的表位,設計、合成CTL、B/Th多表位表達盒。以H5HA、H7HA、H1NP、多表位表達盒為主要目的基因,pVAX1為載體構建用來預防H5、H7、H1、H3亞型流感的多表位核酸疫苗。將所構建的疫苗載體轉(zhuǎn)染BHK細胞,通過RT-PCR和IFA驗證核酸疫苗抗原成分可以在真核細胞中成功表達。利用小鼠作為哺乳動物模型,對所構建的復合多表位核酸疫苗免疫原性進行研究,表明構建的核酸疫苗在誘導細胞免疫及體液免疫方面具有顯著優(yōu)勢。 本實驗的創(chuàng)新之處在于:1)依靠H5、H7亞型流感主要抗原成分,結合H1、H3抗原的功能表位構建了一種新型復合多表位核酸疫苗,目的是通過疫苗接種來預防H5、H7、H1、H3多種亞型流感病毒;2)預測多條H1、H3亞型流感功能表位,并將表位設計成能夠發(fā)揮功能的多表位表達盒;3)通過小鼠實驗免疫評價構建核酸疫苗的免疫原性。
[Abstract]:Influenza is an infectious disease caused by influenza virus, with fever, mucosal congestion and acute respiratory symptoms. The incidence of the disease is high and destructive. Since the invention of influenza vaccine in 1930s, 25 ~ 500000 people still die from influenza every year. Seasonal influenza mainly consists of H _ 1 H _ 3 subtype, and avian influenza H _ 5 H _ 5 H _ 7 subtype also presents human infection cases. Influenza viruses are mutating and could evolve into pandemic strains at any time. Many countries around the world are developing new influenza vaccines to cope with multiple subtypes of influenza pandemics. In this study, using bioinformatics and immunological knowledge, the T cell epitopes of H1H3 subtype influenza virus were predicted and screened. Three CTL epitopes: H3HA545-553H3HA546-554H3NP189-1979B and Th cell epitopes were obtained. Combined with the published epitopes, CTL B / T h multiepitope expression cassette was designed and synthesized. The multiepitope nucleic acid vaccine against H5, H7, H1, H1 and H3 subtype influenza was constructed by using H5 H7 H7 HAH1 NP1 and multiepitope expression cassette as main target gene pVAX1 as vector for the prevention of H5, H7, H1, H1, H1, H1, H3 subtype influenza. The constructed vaccine vector was transfected into BHK cells. RT-PCR and IFA were used to verify that the antigen components of nucleic acid vaccine could be successfully expressed in eukaryotic cells. The immunogenicity of the complex polyepitope nucleic acid vaccine was studied by using mouse as a mammalian model. The results showed that the constructed nucleic acid vaccine had significant advantages in inducing cellular and humoral immunity. The innovation of this experiment is that a novel compound polyepitope nucleic acid vaccine was constructed based on the main antigen components of H5 and H7 subtype influenza and the functional epitopes of H1H3 antigen. The aim of this study was to predict multiple functional epitopes of H1 / H3 subtype influenza virus by vaccinating against H5 / H7 / H1 / H1 / H3 subtype influenza viruses. The immunogenicity of nucleic acid vaccine was evaluated by mouse experimental immunization.
【學位授予單位】：吉林大學
【學位級別】：博士
【學位授予年份】：2010
【分類號】：R392

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