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模拟B族链球菌III型荚膜多糖抗原的肽段。

Peptides that mimic the group B streptococcal type III capsular polysaccharide antigen.

作者信息

Pincus S H, Smith M J, Jennings H J, Burritt J B, Glee P M

机构信息

Department of Microbiology, Montana State University, Bozeman 59717-3520, USA.

出版信息

J Immunol. 1998 Jan 1;160(1):293-8.

PMID:9551983
Abstract

Microbial polysaccharides are notably poor immunogens. We have developed an alternate route for the production of Abs to important carbohydrate epitopes. mAb S9, a protective mAb against the type III capsular polysaccharide of group B streptococci (GBS), was used to select epitope analogues from a peptide display phage library. Depending upon desorption conditions, two populations of phage were identified with displayed sequences of WENWMMGNA and FDTGAFDPDWPA. ELISA results demonstrated that these phage bound to S9 and no other Abs. Phage blocked the binding of S9 to type III GBS, but did not block binding by another anti-GBS mAb. Phage displaying the latter peptide sequence showed greater inhibition. Ab S9 and other monoclonal and polyclonal anti-GBS type III antisera bound the synthetic peptide FDTGAFDPDWPAC. The binding of S9 to GBS was inhibited by the free peptide with an IC50 of 30 microg/ml. The binding of polyclonal anti-GBS antibodies to peptide could be blocked by intact GBS as well as purified capsular polysaccharide. The peptide was conjugated to three different carriers and was used to immunize mice. All mice produced a significant antibody response to GBS and to the purified capsular polysaccharide following a single immunization. These data demonstrate that a peptide mimetic of the GBS capsular polysaccharide is both antigenic and immunogenic. The incorporation of such peptides into vaccine preparations may enhance the efficacy of vaccines in inducing Ab responses to important carbohydrate epitopes.

摘要

微生物多糖是明显较差的免疫原。我们已开发出一条替代途径来生产针对重要碳水化合物表位的抗体。单克隆抗体S9是一种针对B族链球菌(GBS)Ⅲ型荚膜多糖的保护性单克隆抗体,用于从肽展示噬菌体文库中筛选表位类似物。根据解吸附条件,鉴定出两个噬菌体群体,其展示的序列分别为WENWMMGNA和FDTGAFDPDWPA。酶联免疫吸附测定(ELISA)结果表明,这些噬菌体与S9结合,而不与其他抗体结合。噬菌体阻断了S9与Ⅲ型GBS的结合,但不阻断另一种抗GBS单克隆抗体的结合。展示后一种肽序列的噬菌体显示出更大的抑制作用。抗体S9以及其他单克隆和多克隆抗GBSⅢ型抗血清与合成肽FDTGAFDPDWPAC结合。游离肽以30微克/毫升的半数抑制浓度(IC50)抑制S9与GBS的结合。完整的GBS以及纯化的荚膜多糖均可阻断多克隆抗GBS抗体与肽的结合。该肽与三种不同的载体偶联,并用于免疫小鼠。所有小鼠在单次免疫后均对GBS和纯化的荚膜多糖产生了显著的抗体反应。这些数据表明,GBS荚膜多糖的肽模拟物具有抗原性和免疫原性。将此类肽掺入疫苗制剂中可能会提高疫苗诱导针对重要碳水化合物表位的抗体反应的效力。

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