HIV1 CB亚型价重组MVA病毒疫苗免疫原性的研究.docx

中国医学科学院北京协和医学院硕士研究生毕业论文摘要 中国医学科学院北京协和医学院硕士研究生毕业论文 摘要 艾滋病在全球的快速传播严重威胁着人们的生命与健康。研制 出一种能有效预防HIV感染和控制HIV病毒复制的HIV疫苗成为当前 科学界的首要任务。痘苗病毒载体是目前倍受关注的新型艾滋病疫苗 载体，它能激发机体产生较强的细胞免疫反应，而CD4+T细胞和 CD8+T细胞在控制HIV复制方面起着重要作用。 本实验中所研究的ADMVA疫苗是以痘苗病毒安卡拉株 (Modified vaccinia Ankara，MvA)为载体；插入了人类免疫缺陷病 毒1型(HIV一1)c／B’亚型的五个基因，分别是env、gag、pol、nef、 tat。 本实验主要研究该疫苗的免疫原性，实验中设立i05pfu／mL、 i06pfu／mL、107pfu／mL ADMVA三个剂量组，用ELISPOT方法检测细胞 免疫反应。同时，以Gag蛋白作为包被抗原，使用间接ELISA的方法 检测体液免疫反应。结果显示免疫后的小鼠对插入基因env、gag、 pol和nef所表达蛋白均产生了特异性细胞免疫应答，且免疫效果与 免疫剂量呈正相关。ELISA结果表明，ADMVA疫苗免疫诱导产生了特 异性体液免疫，抗HIV—IGag的血清抗体滴度与免疫次数和免疫剂量 都存在正相关性。结论：ADMVA疫苗能有效地诱导小鼠产生特异地细 胞免疫和体液免疫反应。 关键词HIV-I c／B’亚型ADMVD疫苗免疫原性 AbstractPeople’S Abstract People’S life and health was threatened seriously with the high spread pace of HIV virus．Affordable therapeutic strategies that induce sustained control of human immunodeficiency virus type I(HIV一1)．replication and prevent HIV infection are urgently needed Vaccinia virus vector was a popular HIV vaccine recently which inducing beRer cellular immune responses．And CD8+and CD4+T cells are crucial to HIV-1 contr01． The obj ect of the research is evaluating the immunogenicity of a recombinant modified vaccinia virus Ankara．vectored vaccine expressing the consensus HIV．1 clade C／B’．Mice were inoculmed with 3-dose HIV vaccine by intramuscular inj ection．B lood sample were collected every second week，and then the antibodies against HIV were detected．At week 6，mice were killed and cellular immune responses were examined by ELISPOT．ResuIt has shown the number of spot forming cells in the 1 07 pfu／mL．dose group was more than those of l 05 pfu／mL．dose and 1 06 pfu／mL．dose groups significantly．HIV specific antibodies emerged at week 2 and elevated rapidly at week 4 and week 6．The level of specific IgG in the 1 07 pfu／mL．dose group was more than those of l 05 pfu／mL ．dose and 1 06 pfu／mL．dose groups significantly．Conclusion The ADMVA induces both humoral immunoresponse and cellular immune responses· Key words：HIV一1 clade C／B’ A