Design of a mimotope-peptide based double epitope vaccine against disseminated candidiasis.
Design of a mimotope-peptide based double epitope vaccine against disseminated candidiasis.
复制标题
基于模拟表位肽的抗播散性念珠菌病双表位疫苗的设计。
DOI：
10.1016/j.vaccine.2019.03.061
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发表时间：
2019
期刊：
影响因子：
5.5
通讯作者：
Eberle,Karen
中科院分区：
文献类型：
--
作者：
Xin,Hong;Glee,Pati;Adams,Abby;Mohiuddin,Farhan;Eberle,Karen
人类血源性播散性念珠菌病是美国医院血液感染的第三大原因。目前还没有FDA批准用于人类的抗真菌疫苗或预防性/治疗性抗体。我们首次报道了针对白色念珠菌细胞表面表位的新型合成肽和糖肽类疫苗，可保护小鼠免受播散性念珠菌病的侵害。我们发现针对肽Fba的抗体(来源于c。白细胞表面蛋白（果糖二磷酸醛缩酶）或forC。白色原细胞表面聚糖表位β- 1,2 -甘露糖[β-(Man)3])都具有保护作用。这是人类传播念珠菌病疫苗设计的重要一步。然而，考虑到低聚糖合成的复杂性，在本研究中，我们采用了一种新的策略，即使用肽模位作为替代糖肽[β-(Man)3-Fba]疫苗的聚糖部分的替代免疫原，结构上模仿具有保护性的聚糖表位β-(Man)3-Fba。所选的五种模型在小鼠中都具有免疫原性，其中三种模型能够诱导小鼠抵抗播散性念珠菌病。此外，用三种米莫托肽结合疫苗免疫也能诱导特异性抗体反应，重要的是，对小鼠播散性念珠菌病有保护作用。因此，我们新设计的基于mimotope-peptide的抗念珠菌病双表位疫苗是一种潜在的候选疫苗，生产经济、高效、安全，可用于人类。
Hematogenously disseminated candidiasis in humans is the third leading cause of nosocomial bloodstream infections in the US. There is no FDA approved antifungal vaccine or prophylactic/therapeutic antibody for use in humans. We first reported novel synthetic peptide and glycopeptide vaccines againstCandida albicanscell surface epitopes that protect mice against disseminated candidiasis. We showed that antibodies specific for the peptide Fba (derived fromC. albicanscell surface protein fructosebisphosphatealdolase) or forC. albicanscell surface glycan epitope β-1, 2–mannotriose [β-(Man)3]) are both protective. This is an important step forward in vaccine design against disseminated candidiasis in humans. However, given the complexity of oligosaccharide synthesis, in this study we performed a new strategy for use of peptide mimotopes that structurally mimic the protective glycan epitope β-(Man)3as surrogate immunogens that substitute for the glycan part of glycopeptide [β-(Man)3-Fba] vaccine. All five selected mimotopes are immunogenic in mice and three mimotopes were able to induce protection in mice against disseminated candidiasis. Furthermore, immunization with three mimotope-peptide conjugate vaccines was also able to induce specific antibody responses, and importantly, protection against disseminated candidiasis in mice. Therefore, our new design of a mimotope-peptide based double epitope vaccine against candidiasis is a potential vaccine candidate that is economical to produce, highly efficacious and safe for use in humans.