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基于计算机预测的利什曼原虫候选肽疫苗的免疫原性和免疫调节作用。

Immunogenicity and immune modulatory effects of in silico predicted L. donovani candidate peptide vaccines.

机构信息

Institute of Endemic Diseases, University of Khartoum, Khartoum, Sudan.

出版信息

Hum Vaccin Immunother. 2012 Dec 1;8(12):1769-74. doi: 10.4161/hv.21881. Epub 2012 Aug 24.

DOI:10.4161/hv.21881
PMID:22922767
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC3656064/
Abstract

Visceral leishmaniasis (VL) is a serious parasitic disease for which control measures are limited and drug resistance is increasing. First and second generation vaccine candidates have not been successful. The goal of the present study was to select possibly immunogenic L. donovani donovani GP63 peptides using immunoinformatics tools and to test their immunogenicity in vitro. The amino acid sequence of L. donovani donovani GP63 [GenBank accession: ACT31401] was screened using the EpiMatrix algorithm for putative T cell epitopes that would bind to the most common HLA class II alleles (DRB11101 and DRB10804) among at-risk populations. Four T cell epitopes were selected from nine potential candidates. Stimulation of whole blood from healthy volunteers using the peptides separately produced mean IFN-γ and IL-4 levels that were not significantly different from negative controls, while the pooled peptides produced a moderate IFN-γ increase in some volunteers. However, mean IL-10 levels were significantly reduced for all individuals compared with controls. The immunogenicity of these epitopes may be harnessed most effectively in a vaccine delivered in combination with immune-modulating adjuvants.

摘要

内脏利什曼病(VL)是一种严重的寄生虫病,其控制措施有限,且耐药性正在增加。第一代和第二代疫苗候选物都没有成功。本研究的目的是使用免疫信息学工具选择可能具有免疫原性的利什曼原虫 GP63 肽,并在体外测试其免疫原性。使用 EpiMatrix 算法筛选利什曼原虫 GP63 [GenBank 登录号:ACT31401]的氨基酸序列,以寻找可能与高危人群中最常见的 HLA Ⅱ类等位基因(DRB11101 和 DRB10804)结合的 T 细胞表位。从九个潜在候选物中选择了四个 T 细胞表位。单独使用这些肽刺激健康志愿者的全血产生的 IFN-γ 和 IL-4 水平与阴性对照没有显著差异,而混合肽在一些志愿者中产生了适度的 IFN-γ 增加。然而,与对照组相比,所有个体的平均 IL-10 水平均显著降低。与免疫调节佐剂联合使用疫苗可以最有效地利用这些表位的免疫原性。

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A prime/boost DNA/Modified vaccinia virus Ankara vaccine expressing recombinant Leishmania DNA encoding TRYP is safe and immunogenic in outbred dogs, the reservoir of zoonotic visceral leishmaniasis.一种表达编码TRYP的重组利什曼原虫DNA的初免/加强DNA/改良安卡拉痘苗病毒疫苗,在人畜共患内脏利什曼病的储存宿主杂种犬中是安全且具有免疫原性的。
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