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通过自佐剂糖脂肽评估 A 组菌细胞壁碳水化合物的免疫原性。

Immunogenicity Assessment of Cell Wall Carbohydrates of Group A via Self-Adjuvanted Glyco-lipopeptides.

机构信息

School of Chemistry and Molecular Biosciences, The University of Queensland, St. Lucia, QLD 4072, Australia.

Institute for Molecular Bioscience, The University of Queensland, St. Lucia, QLD 4072, Australia.

出版信息

ACS Infect Dis. 2021 Feb 12;7(2):390-405. doi: 10.1021/acsinfecdis.0c00722. Epub 2021 Feb 3.

Abstract

Identifying the immunogenic moieties and their precise structure of carbohydrates plays an important role for developing effective carbohydrate-based subunit vaccines. This study assessed the structure-immunogenicity relationship of carbohydrate moieties of a single repeating unit of group A carbohydrate (GAC) present on the cell wall of group A (GAS) using a rationally designed self-adjuvanted lipid-core peptide, instead of a carrier protein. Immunological evaluation of fully synthetic glyco-lipopeptides (particle size: 300-500 nm) revealed that construct consisting of higher rhamnose moieties (trirhamnosyl-lipopeptide) was able to induce enhanced immunogenic activity in mice, and GlcNAc moiety was not found to be an essential component of immunogenic GAC mimicked epitope. Trirhamnosyl-lipopeptide also showed 75-97% opsonic activity against four different clinical isolates of GAS and was comparable to a subunit peptide vaccine (J8-lipopeptide) which illustrated 65-96% opsonic activity.

摘要

确定碳水化合物的免疫原性部分及其确切结构对于开发有效的基于碳水化合物的亚单位疫苗至关重要。本研究使用经过合理设计的自佐剂脂质核心肽,而不是载体蛋白,评估了 A 组(GAS)细胞壁上单个 A 组碳水化合物(GAC)重复单元上的碳水化合物部分的结构-免疫原性关系。对全合成糖脂肽(粒径:300-500nm)的免疫学评估表明,由较高鼠李糖部分(三鼠李糖基脂肽)组成的构建体能够在小鼠中诱导增强的免疫原性活性,并且 GlcNAc 部分不是模拟免疫原性 GAC 表位的必需成分。三鼠李糖基脂肽对四种不同的 GAS 临床分离株也表现出 75-97%的调理活性,与亚单位肽疫苗(J8-脂肽)相当,其显示 65-96%的调理活性。

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