IMMUNIZATION WITH ANTIGENIZED VECTORS

使用抗原化载体进行免疫接种

• 批准号: 6543436
• 负责人: Swey-Shen Chen
• 金额: $ 25.06万
• 依托单位: INSTITUTE OF GENETICS
• 依托单位国家: 美国
• 财政年份: 2001
• 资助国家: 美国
• 起止时间: 2001-05-03 至 2002-10-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6543436
• 关键词: B lymphocyte; antibody formation; antiidiotype antibody; chemical models; conformation; cytotoxic T lymphocyte; helper T lymphocyte; immunoglobulin E; immunoglobulin genes; laboratory mouse; mast cell; nonhuman therapy evaluation; nucleic acid probes; nucleic acid sequence; oligonucleotides; protein structure; recombinant proteins; transfection /expression vector; vaccine development; vector vaccine

DESCRIPTION: (Adapted from the Investigator's abstract): Regulation of IgE production by B cells is orchestrated by Th2 cytokine IL-4, and cognate interaction of B cells and Th2 via CD4O and CD4OL. IL-4 and CD40L mediate IgE gene rearrangement, and activation of IgE-committed B cells. IL-4 in turn sustains IgE production by skewing Th2 development. This paradigm dictates a treatment modality based on measures to diminish endogenous levels of IL-4 and thereby IgE production by IgE-committed B cells. Alternatively, anti-IgE is employed to inhibit IgE production by IgE-committed B cells. Studies from our laboratoryand that of Nisonoff established an animal model of pan-IgE deficiency in mice perinatally immunized with IgE, prior to the onset of self-tolerance to IgE molecules. Anti-IgE was implicated to play an important role in inhibiting IgE production of IgE committed B cells. This applicationwill determine whether therapeutically useful anti-IgE can be elicited in adult mice immunized with IgE B and T cell epitopes in the presence of strong costimulation. Recently, exciting progress has been made in engineering antigenized immunoglobulin vectors that incorporate oligonucleotides corresponding to both B and T cell epitopes, and GM-CSF as costimulator. Importantly, cloned and expressed B cell epitopes exhibit native conformation of the protein antigens, while T cell epitopes can be processed and presented by GM-CSF activated APC. IgE vaccines prepared in the antigenized vector, pCDR3 will be employed in the proposed studies. Our short-term goal is to achieve the following three Aims: Aim I. To Determine Native Conformation IgE B Cell Epitopes, and Induce Pan-IgE Deficiency by Breaking Self Tolerance to IgE B Cell Epitopes in Adult Mice Immunized with IgE Vaccines. Aim II. To Determine Immunodominant, Physiological IgE helper T Cell Epitopes, and Induce PersistentPan-IgE Deficiency by Breaking Self Tolerance to IgE T and B Cell Epitopes in Concert in Adult Mice Immunized with IgE Vaccines. Aim III. To Determine Mechanisms of Anti-IgE-Mediated Inhibition of IgE Production by IgE-CommittedB Cells in vitro.

描述：(改编自调查人员摘要)：调节免疫球蛋白E B细胞的产生受Th2细胞因子IL-4和同源物的调控 B细胞与Th2细胞通过CD4O和CD4OL相互作用。IL-4和CD40L介导的IgE 基因重排和IgE承诺的B细胞的激活。依次为IL-4 通过扭曲Th2的发育来维持IgE的产生。这个范例规定了一个 基于降低内源性IL-4和IL-4水平措施的治疗方式 因此，IgE承诺的B细胞产生IgE。或者，抗IgE是 被用来抑制IgE承诺的B细胞产生IgE。来自我们的研究 实验室和Nisonoff建立了PAN-IgE的动物模型 围产期免疫的小鼠在发病前出现的缺陷 自身对IgE分子的耐受性。抗-IgE被牵连起了重要的作用 抑制IgE分泌的B细胞产生IgE的作用。 这一应用将确定抗IgE是否可以在治疗上有用 IgE B和T细胞表位免疫成年小鼠的研究 强烈的共刺激作用。最近，在以下方面取得了令人振奋的进展 重组抗原化免疫球蛋白载体 与B和T细胞表位相对应的寡核苷酸和GM-CSF AS 共刺激因子。重要的是，克隆和表达的B细胞表位展示了天然的 蛋白质抗原的构象，而T细胞表位可以处理 并由GM-CSF激活的APC提呈。在抗原化中制备的免疫球蛋白疫苗 在拟议的研究中，将使用载体pCDR3。我们的短期目标是 实现以下三个目标： 目的I.确定天然构象的IgE B细胞表位，并诱导泛IgE 成年小鼠打破自身对IgE B细胞表位耐受性的缺陷 接种免疫球蛋白E疫苗。 目的II.确定免疫优势的生理性IgE辅助性T细胞表位， 通过打破自身对IgE和T的耐受性而诱导持续性泛IgE缺乏症 IgE疫苗免疫成年小鼠体内B细胞表位的研究 目的III.确定抗IgE介导的抑制IgE的机制 体外培养的免疫球蛋白B细胞产生。

项目成果

Selection of antigenic markers on a GFP-Ckappa fusion scaffold with high sensitivity by eukaryotic ribosome display.

通过真核核糖体展示高灵敏度地选择 GFP-Ckappa 融合支架上的抗原标记。

• DOI: 10.1016/j.bbrc.2007.05.083
• 发表时间: 2007
• 期刊: Biochemical and biophysical research communications
• 影响因子: 3.1
• 作者: Yang,Yong-Min;Barankiewicz,TeresaJ;He,Mingyue;Taussig,MichaelJ;Chen,Swey-Shen
• 通讯作者: Chen,Swey-Shen