ev71减毒活疫苗的研发和减毒机制的研究病原生物学专业论文.docxVIP

北京协和医学院硕士研究生毕业论文提示：恒河猴婴猴可作为EV71减毒活疫苗评价的敏感动物模型，而乳鼠并不是最佳 北京协和医学院硕士研究生毕业论文 提示：恒河猴婴猴可作为EV71减毒活疫苗评价的敏感动物模型，而乳鼠并不是最佳 的动物模型；FY23．K株35℃低温传至第28代，毒株仍未达到理想的减毒株要求，需 继续进行减毒工作。 (6)与原始代次相比，FY23．K毒株经35。C传代培养至第25代后全基因组共有48个 碱基突变，这些突变也都存在于第35代及37C的第33代和50代，这些碱基的突变导致 了10个氨基酸的变异，均有可能是毒株致病性减弱的原因；并初步推测VPl第145 位可能是EV71的一个毒力相关位点，从谷氨酸变为谷氨酰胺，可以减弱EV71的毒 力。 关键词：EV71；减毒活疫苗；减毒机制；乳鼠致病性；动物模型； 3 万方数据 北京协和医学院硕士研究生毕业论文Development 北京协和医学院硕士研究生毕业论文 Development of EV7 1 live attenuated vaccines and the attenuation mechanism research Hand．foot and mouth disease(HFMD)has become a global widespread acute infectious discase．Enterovirus 71(EV7 1)is of the main pathogens，which mainly infect infants and young children under the age of five，and it can cause severe in minority of patients with neurological syndrome，or even lead to death．In recent years， There were a lot of research about EV7 1 attenuated vaccine and attenuated mechanism， but it was not fully difined。How to reduce the virulence of EV7 1 and evaluate its virulence decrease iS pivotal in attenuated EV7 1 vaccine research． In this paper,we separated one EV7 1 strain from many clinical samples，which has higher infectious titers and could make 1 00％suckling mouse dead．after five generation serial passaging in vivo，we found that there was no significant decrease of pathogenicity to the suckling mice，But compared with the second generation，the time for virus of the fifth generation making the KMB 1 7 lesion completely was significantly extended．It means that the adaptability of virus in KMB 1 7 decreased after successive batches in the suckling mice．While，alternating passaging to the fourth generation，the pathogenicity of the the strain has weak decreasing trend． According to the study of FY23一K strain passaging in different temperature and ways in vitro，we found： (1)after serial passaging in KMB 1 7 cells at 3 3℃，the strain’S infectious titers decreased gradually．the time to reach 75％cytopathic effect delayed with passaging； while at 3 5。C，viruses were