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HIV-1 Consensus Envelope-Induced Broadly Binding Antibodies

机译:HIV-1共识包络诱导宽染色抗体

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摘要

Antibodies that cross-react with multiple HIV-1 envelopes (Envs) are useful reagents for characterizing Env proteins and for soluble Env capture and purification assays. We previously reported 10 murine monoclonal antibodies induced by group M consensus Env, CON-6 immunization. Each demonstrated broad cross-reactivity to recombinant Envs. Here we characterized the Env epitopes to which they bind. Seven mapped to linear epitopes in gp120, five at the Env N-terminus, and two at the Env C-terminus. One antibody, 13D7, bound at the gp120?N-terminus (aa 30–42), reacted with HIV-1-infected CD4 + T cells, and when expressed in a human IgG1 backbone, mediated antibody-dependent cellular cytotoxicity. Antibody 18F11 bound at the gp120 C-terminus (aa 445–459) and reactivity was glycan dependent. Antibodies 13D7, 3B3, and 16H3 bound to 100 percent of HIV-1 Envs tested in ELISA and sodium dodecyl sulfate/polyacrylamide gel electrophoresis/western blot analysis. These data define the epitopes of monoclonal antibody reagents for characterization of recombinant Envs, one epitope of which is also expressed on the surface of HIV-1-infected CD4 + T cells.
机译:与多个HIV-1包络(ENVS)交叉反应的抗体是用于表征ENV蛋白的有用试剂和可溶性型ENV捕获和纯化测定。我们以前报道了由M组共识env,Con-6免疫诱导的10只小鼠单克隆抗体。每个都表现出与重组envs的广泛反应性。在这里,我们的特征是它们与之结合的env表现。七个映射到GP120的线性表位,在Env n-terminus处的五个,并且在Env C-Terminus处。在GP120αn-末端(AA 30-42)的一抗13d7,与HIV-1感染的CD4 + T细胞反应,并且当以人IgG1骨架表达时,介导的抗体依赖性细胞细胞毒性。在GP120 C-末端(AA 445-459)中结合的抗体18F11和反应性是甘油依赖性。在ELISA和十二烷基硫酸钠/聚丙烯酰胺凝胶电泳/ Western印迹分析中,抗体13d7,3b3和16h3结合至100%的HIV-1 ENV,硫酸钠/聚丙烯酰胺凝胶电泳/ Western印迹分析。这些数据定义了单克隆抗体试剂的表位,用于表征重组环境,其表位也在HIV-1感染的CD4 + T细胞表面上表达。

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  • 作者单位

    Duke Human Vaccine Institute Duke University School of Medicine Durham North Carolina.;

    Duke Human Vaccine Institute Duke University School of Medicine Durham North Carolina.;

    Duke Human Vaccine Institute Duke University School of Medicine Durham North Carolina.;

    Duke Human Vaccine Institute Duke University School of Medicine Durham North Carolina.;

    Duke Human Vaccine Institute Duke University School of Medicine Durham North Carolina.;

    Department of Immunology Duke University School of Medicine Durham North Carolina.;

    Duke Human Vaccine Institute Duke University School of Medicine Durham North Carolina.;

    Duke Human Vaccine Institute Duke University School of Medicine Durham North Carolina.;

    Duke Human Vaccine Institute Duke University School of Medicine Durham North Carolina.;

    Duke Human Vaccine Institute Duke University School of Medicine Durham North Carolina.;

    Duke Human Vaccine Institute Duke University School of Medicine Durham North Carolina.;

    Duke Human Vaccine Institute Duke University School of Medicine Durham North Carolina.;

    Duke Human Vaccine Institute Duke University School of Medicine Durham North Carolina.;

    Duke Human Vaccine Institute Duke University School of Medicine Durham North Carolina.;

    Duke Human Vaccine Institute Duke University School of Medicine Durham North Carolina.;

    Duke Human Vaccine Institute Duke University School of Medicine Durham North Carolina.;

    Los Alamos National Laboratory Los Alamos New Mexico.;

    Duke Human Vaccine Institute Duke University School of Medicine Durham North Carolina.;

    Duke Human Vaccine Institute Duke University School of Medicine Durham North Carolina.;

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  • 正文语种 eng
  • 中图分类 传染病;
  • 关键词

    antibody-mediated immunity; HIV; monoclonal; vaccine design; ADCC;

    机译:抗体介导的免疫;艾滋病毒;单克隆;疫苗设计;ADCC;

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