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Studies of peptide mimicry of the group B streptococcus type III capsular polysaccharide antigen.

机译：B组链球菌III型荚膜多糖抗原的肽模拟研究。

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摘要

Capsular polysaccharide (CPS) of Streptococcus group B (GBS) is a poor immunogen and functions as T cell independent antigen, eliciting low IgG antibody with deficient immunologic memory. We previously identified a peptide, S9, which mimics CPS of type III GBS. Here we have taken steps to develop the mimetic peptide as a vaccine against GBS group III. We enhanced the immunogenicity of the peptide by presenting it on the coat protein of Cowpea Chlorotic Mottle Virus (CCMV). And we searched for better mimetic peptides by constructing a secondary phage display library. To accomplish the first goal, DNA encoding S9 was cloned into five constructions CCMV coat protein loops using recombinant DNA techniques. The results indicated that inserting the S9 peptide sequence into CCMV coat protein loops disrupted virus and virus-like particle assembly. Therefore the S9 peptide was conjugated to CCMV coat protein using chemical linkers. The CCMV-S9 conjugation products remained intact as monomer virions. Mice were immunized with the CCMV-S9, SubE-S9 (a mutant that does not assemble virions), CPMV-S9 (S9 conjugated to Cowpea Mosaic Virus) and S9 conjugated to the carrier protein KLH, with and without Freund's adjuvant. The CCMV-S9, CPMV-S9 and KLH-S9 induce anti-S9 antibody even without the adjuvant whereas SubE-S9 induced an anti-S9 response only with adjuvant. The CCMV-S9 and CPMV-S9 predominantely induced a Th1 response with antigen-specific IgG2a and IFN-gamma production, whereas the KLH-S9 predominantly induced a Th2 response with antigen-specific IgG1 and IL4/IL10 production. To accomplish the second goal, a DNA sublibrary was designed to have approximately one mutation in each displayed peptide sequence. Peptides with higher affinity to the S9 mAb were identified by affinity selection. ELISA analysis from randomly selected phage clones indicated that amino acid residues 3-5 and 7-10 of S9 peptide are important in specific binding activity to S9 monoclonal antibody. These studies identified peptides with greater affinity for the selecting antibody, i.e. enhanced antigenicity.
机译：B链球菌（GBS）的荚膜多糖（CPS）免疫原性较差，并起T细胞非依赖性抗原的作用，引发免疫功能低下的低IgG抗体。我们之前鉴定了一种肽S9，它可以模拟III型GBS的CPS。在这里，我们已采取步骤开发模拟肽作为针对GBS III组的疫苗。通过将其呈现在Cow豆绿斑驳病毒（CCMV）的外壳蛋白上，我们增强了该肽的免疫原性。我们通过构建二级噬菌体展示文库来寻找更好的模拟肽。为了实现第一个目标，使用重组DNA技术将编码S9的DNA克隆到5个CCMV外壳蛋白环结构中。结果表明，将S9肽序列插入CCMV外壳蛋白环中会破坏病毒和病毒样颗粒的装配。因此，使用化学接头将S9肽缀合至CCMV外壳蛋白。 CCMV-S9偶联产物仍完整保留为单体病毒体。在有和没有弗氏佐剂的情况下，用CCMV-S9，SubE-S9（不组装病毒体的突变体），CPMV-S9（与Cow豆花叶病毒缀合的S9）和与载体蛋白KLH缀合的S9免疫小鼠。 CCMV-S9，CPMV-S9和KLH-S9甚至在没有佐剂的情况下也诱导抗S9抗体，而SubE-S9仅在佐剂的情况下诱导抗S9反应。 CCMV-S9和CPMV-S9主要诱导抗原特异性IgG2a和IFN-γ产生的Th1反应，而KLH-S9主要诱导抗原特异性IgG1和IL4 / IL10产生的Th2反应。为了实现第二个目标，设计了一个DNA子库，使每个显示的肽序列具有大约一个突变。通过亲和力选择鉴定出对S9 mAb具有更高亲和力的肽。从随机选择的噬菌体克隆的ELISA分析表明，S9肽的氨基酸残基3-5和7-10在与S9单克隆抗体的特异性结合活性中很重要。这些研究鉴定了对选择抗体具有更大亲和力的肽，即增强的抗原性。

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  • 作者

    Pomwised, Rattanaruji.;

  • 作者单位

    Montana State University.$bMicrobiology.;

  • 授予单位 Montana State University.$bMicrobiology.;
  • 学科 Biology Microbiology.
  • 学位 Ph.D.
  • 年度 2007
  • 页码 253 p.
  • 总页数 253
  • 原文格式 PDF
  • 正文语种 eng
  • 中图分类 微生物学;
  • 关键词

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