Peptide adjacent to glycosylation sites impacts immunogenicity of glycoconjugate vaccine.
Peptide adjacent to glycosylation sites impacts immunogenicity of glycoconjugate vaccine.
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与糖基化位点相邻的肽会影响糖缀合物疫苗的免疫原性。
DOI：
10.18632/oncotarget.19944
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发表时间：
2018-01-02
期刊：
影响因子：
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通讯作者：
Chen M
中科院分区：
文献类型：
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作者：
Ma Z;Zhang H;Wang PG;Liu XW;Chen M
糖缀合物疫苗是由多糖与载体蛋白共价连接而成。糖基化位点选择作为导致糖缀合物结构异质性的重要因素，其对糖缀合物疫苗免疫原性的影响越来越受到人们的关注。为了阐明糖基化连接与糖结合疫苗免疫原性的关系，本研究采用免疫荧光法检测了抗E。coliO 157：H7糖偶联物O-PS-MBP，合成了三个肽段GS 1、GS 2、GS 3。免疫原性结果表明，只有邻近糖基化位点的肽（GS 1和GS 2）才能促进PS特异性IgG抗体的产生，并有助于PS特异性IgG亚类的分布。此外，GS 1和GS 2具有显著的引发效应，引发PS特异性IgG抗体。这些结果表明，糖基化位点的不同可导致肽和糖肽在抗原递呈细胞上的差异，从而影响糖缀合物疫苗的免疫原性。这些结果拓展了目前对糖缀合物疫苗激活适应性免疫系统机制的认识，对合理设计糖缀合物疫苗具有重要意义。
Glycoconjugate vaccine is composed of polysaccharides (PSs) covalently linked with carrier protein. Glycosylation site selection, as a significant factor leading to heterogeneities of glycoconjugate structure, draws more and more attentions for its impact on the immunogenicity of glycoconjugate vaccine. To elucidate the relationship between glycosylation connectivity and immunogenicity of glycoconjugate vaccine, in this study, anti-E. coli O157:H7 glycoconjugate O-PS-MBP with defined connectivity, and three selected peptide segments GS1, GS2, GS3 derived from O-PS-MBP was synthesized. Immunogenicity results showed that only peptides adjacent to the glycosylation sites (GS1 and GS2) promoted the generation of PS-specific IgG antibodies and contributed to PS-specific IgG subclass distribution. Furthermore, GS1 and GS2 had significant priming effect for eliciting PS-specific IgG antibodies. These results indicated that different locations of glycosylation sites could lead to diverse presentation of peptides and glycopeptides to APCs and influence the immunogenicity of glycoconjugate vaccine, which extend the current understanding of mechanism for adaptive immune system activation by glycoconjugate vaccine, and have implications for rational glycoconjugate vaccine design.