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首页> 外文期刊>Proceedings of the National Academy of Sciences of the United States of America >Synthetic glycopeptide vaccines combining β-mannan and peptide epitopes induce protection against candidiasis
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Synthetic glycopeptide vaccines combining β-mannan and peptide epitopes induce protection against candidiasis

机译：结合β-甘露聚糖和肽表位的合成糖肽疫苗可诱导预防念珠菌病

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摘要

The first fully synthetic glycopeptide vaccines against a fungal disease have been used to combat disseminated candidiasis in mice. Six T cell peptides found in Candida albicans cell wall proteins were selected by algorithm peptide epitope searches; each was synthesized and conjugated to the fungal cell wall β-mannan trisaccharide [β-(Man)_3] by novel saccharide-peptide linker chemistry to create glycopeptide conjugates. The six proteins were selected because of expression during human candidiasis and cell wall association and included: fructose-bisphosphate aldolase (Fba); methyltetrahydropteroyltriglutamate (Met6); hyphal wall protein-1 (Hwp1); enolase (Enol); glyceraldehyde-3-phosphate de-hydrogenase (Gap1); and phosphoglycerate kinase (Pgk1). By immunization protocols favoring production of protective antibody, the β-(Man)_3-Fba, β-(Man)_3-Met6 and β-(Man)_3-Hwp1 induced protection evidenced by survival and reduced kidney fungal burden, the β-(Man)_3-Eno1 and β-(Man)_3-Gap1 gave moderate protection, and the β-(Man)_3-Pgk1 slightly enhanced disease. For the β-(Man)_3-Fba conjugate, protection was uniquely acquired through immunity against the carbohydrate and the Fba peptide. This approach based on fully synthetic chemically defined immunogens should be generally useful in vaccine development.
机译：第一种针对真菌疾病的全合成糖肽疫苗已被用于对抗小鼠中传播的念珠菌病。通过算法肽表位搜索选择在白色念珠菌细胞壁蛋白中发现的6个T细胞肽；通过新颖的糖-肽接头化学方法，将它们各自合成并缀合到真菌细胞壁β-甘露聚糖三糖[β-（Man）_3]，以创建糖肽缀合物。选择六种蛋白是因为在人念珠菌病期间表达和细胞壁结合，包括：果糖-双磷酸醛缩醛糖醛缩酶（Fba）；四氢蝶呤三谷氨酸甲酯（Met6）;菌丝壁蛋白1（Hwp1）;烯醇化酶（Enol）; 3-磷酸​​甘油醛脱氢酶（Gap1）;和磷酸甘油酸激酶（Pgk1）。通过有利于产生保护性抗体的免疫方案，β-（Man）_3-Fba，β-（Man）_3-Met6和β-（Man）_3-Hwp1诱导了保护作用，这可通过生存和减轻肾脏真菌负担来证明， （Man）_3-Eno1和β-（Man）_3-Gap1提供了中等程度的保护，而β-（Man）_3-Pgk1则稍微增强了疾病。对于β-（Man）_3-Fba缀合物，通过针对碳水化合物和Fba肽的免疫力获得了独特的保护。这种基于完全合成的化学确定的免疫原的方法通常应在疫苗开发中有用。

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