靶向诱导GPG抗体及基序免疫概念论证

发布时间：2018-03-28 20:19

本文选题：HIV-1　切入点：基序免疫　出处：《南京大学》2012年硕士论文

【摘要】：目前HIV疫苗研发的主要障碍之一是病毒膜蛋白的高度突变。从感染者体内筛选的抗血清和通过免疫诱导的抗血清的表位大多是针对具较高免疫原性的高突变的氨基酸区域,很难获得针对高度保守但弱免疫原性区域的表位抗体。位于HIV-1膜蛋白gp120V3可变区顶端的GPGR是病毒主要中和靶位(PND)的主要组成部分。无论是病毒感染或各类病毒膜蛋白抗原诱导的抗体均能有效诱导针对GPGR的抗体。但R的高度可变性直接限制了PND作为艾滋病疫苗靶标的可能性。GPG位于HIV V3环的顶端,是一个高度保守但弱免疫原性的三个连续氨基酸,至今未有针对GPG表位的抗体。本文创造性的运用基序免疫构建了一条由15个氨基酸组成的含有三个连续的氨基酸(GPG)的肽库,成功地在小鼠和兔子体内诱导了高滴度的针对GPG表位广谱中和HIV抗体。并通过杂交瘤技术,获得针对GPG表位具有广谱中和活性的单克隆抗体。同样使用基序免疫设计原则,我们成功的获得了针对HIV V2环和gp41近膜区的高度保守但弱免疫原性的表位抗体。流感病毒和丙型肝炎病毒同样是高突变的病原微生物,研究如何诱导针对高度保守表位的抗体也一直是疫苗研发的重点；我们通过基序免疫成功地诱导了特异性针对这两种病原微生物的保守表位抗体。本文还诱导了针对常规蛋白(鸡卵清白蛋白)的表位抗体。总之基序免疫具有广泛的适用性,能靶向诱导任何氨基酸构成的表位抗体。
[Abstract]:One of the main obstacles of HIV vaccine development is currently the virus membrane protein from infected height mutation. In vivo screening of antisera and induced by immune antiserum epitope mostly for high mutation amino acid region of high immunogenicity, it is difficult to obtain the highly conserved epitope of antibody but weakly immunogenic region. Located in the HIV-1 membrane protein gp120V3 variable region at the top of the GPGR virus (PND) and the main target of the main part. Both antibodies induced by viral infection or various virus membrane protein antigen can effectively induce antibodies against GPGR. But the high variability of R directly limits the PND top as the.GPG target in the possibility of AIDS vaccine HIV V3 ring, is a highly conserved but weak immunogenicity of three consecutive amino acids, has not been for GPG epitope antibody. The paper creatively used motif immune construction A composed of 15 amino acids containing three consecutive amino acid (GPG) of the peptide library successfully in mice and rabbits in vivo induced high titer against GPG epitope broadly neutralizing HIV antibody. Then by hybridoma technique, obtained for single clone antibody GPG epitope has broad-spectrum neutralizing activity also. The use of immune motif design principle, we obtain the highly conserved juxtamembrane region HIV V2 ring and gp41 but weakly immunogenic epitope antibody. The influenza virus and hepatitis C virus is also a pathogenic microorganism of high mutation research how to induce antibodies against highly conserved epitopes also has been the focus of vaccine research and development; we successfully induced immune motif specific conservative form for the two kinds of pathogenic microorganisms the antibody. This paper also induced the conventional protein (ovalbumin) epitope antibody. In short motif free The epidemic is widely applicable and can target the epitopes of any amino acid.

【学位授予单位】：南京大学
【学位级别】：硕士
【学位授予年份】：2012
【分类号】：R392

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