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：（改编自研究者摘要）：IgE的调节 B细胞的产生由Th 2细胞因子IL-4协调， B细胞和Th 2通过CD 4 O和CD 4 OL相互作用。IL-4和CD 40 L介导IgE 基因重排和IgE定型B细胞的活化。IL-4依次 通过扭曲Th 2的发育来维持IgE的产生。这种模式要求 基于降低内源性IL-4水平的措施的治疗方式， 从而通过IgE定型B细胞产生IgE。或者，抗IgE是 用于抑制IgE定型B细胞产生IgE。我们的研究 实验室和Nisonoff建立了泛IgE动物模型 在发病之前， 对IgE分子的自身耐受性。抗IgE被认为是一种重要的 抑制IgE定型B细胞的IgE产生的作用。 本申请将确定是否可以使用治疗上有用的抗IgE抗体。 在用IgE B和T细胞表位免疫的成年小鼠中， 强烈的共刺激。最近，取得了令人兴奋的进展， 工程化抗原化免疫球蛋白载体， 对应于B和T细胞表位的寡核苷酸，以及作为 共刺激分子重要的是，克隆和表达的B细胞表位表现出天然的 蛋白抗原的构象，而T细胞表位可以被加工 由GM-CSF激活的APC提呈。免疫球蛋白E疫苗在抗原化的 载体pCDR 3将用于拟定的研究。我们的短期目标是 实现以下三个目标： 艾姆岛确定天然构象IgE B细胞表位并诱导泛IgE 成年小鼠IgE B细胞表位自身耐受性破坏所致缺陷 免疫IgE疫苗。 Aim II.确定免疫显性、生理性IgE辅助T细胞表位， 通过破坏对IgE T的自身耐受性诱导持续性泛IgE缺乏症， 免疫球蛋白E疫苗免疫的成年小鼠中一致的B细胞表位。 Aim III.确定抗IgE介导的IgE抑制机制 通过体外IgE-致敏细胞的生产。

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