Immunogenic Consensus Sequence T helper Epitopes for a Pan-Burkholderia Biodefense Vaccine
Immunogenic Consensus Sequence T helper Epitopes for a Pan-Burkholderia Biodefense Vaccine
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泛伯克霍尔德杆菌生物防御疫苗的免疫原性共识序列 T 辅助表位
DOI：
10.4172/1745-7580.1000043
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发表时间：
2011
期刊：
影响因子：
--
通讯作者：
W. Martin
中科院分区：
文献类型：
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作者：
Anne Searls De Groot;M. Ardito;L. Moise;Eric Gustafson;D. Spero;Gloria Tejada;W. Martin
由于B类生物恐怖制剂假马利氏伯克霍尔德菌（BPM）和马勒氏伯克霍尔德菌（BM）极易被恐怖分子获取，且具有强大的武器化潜力，因此需要针对它们的生物防御疫苗。伯克霍尔德菌（BC）是一种相关病原体，可引起囊性纤维化患者慢性肺部感染。由于BPM、BM和BC都是细胞内细菌，它们是T细胞疫苗的极佳靶点。然而，大量可用的基因组数据需要免疫信息学的帮助来设计疫苗。使用EpiMatrix、ClustiMer和EpiAssembler（一套免疫信息学疫苗设计工具），我们筛选了31个可用的伯克氏菌基因组，并对我们选择的基于表位的伯克氏菌多病原体疫苗进行了初步测试。结果对31个伯克霍尔德氏菌基因组进行免疫信息学分析，得到350,004个9-mer候选疫苗肽，其中133,469个在10个BM基因组中完全保守，175,722个在11个BPM基因组中完全保守，40,813个在10个BC基因组中完全保守。EpiMatrix进一步筛选得到54,010个高分II类表位；这些被组装成2880个更长的高度保守的“免疫原性共识序列”T辅助表位。100%的肽在体外与至少一个HLA II类等位基因结合，92.7%与至少两个等位基因结合，82.9%与三个等位基因结合，75.6%的结合结果与免疫信息学分析一致。结论我们的研究结果表明，可以快速鉴定在多种伯克霍尔德菌中保守的混杂T辅助表位，并在体外测试它们与HLA配体的结合。下一步，我们将利用BC、BPM感染者的外周血白细胞在体外测试抗原表位，并在人HLA转基因小鼠中测试免疫原性。我们期望这种方法将导致开发一种可许可的泛伯克氏菌生物防御疫苗。
Background Biodefense vaccines against Category B bioterror agents Burkholderia pseudomallei (BPM) and Burkholderia mallei (BM) are needed, as they are both easily accessible to terrorists and have strong weaponization potential. Burkholderia cepaciae (BC), a related pathogen, causes chronic lung infections in cystic fibrosis patients. Since BPM, BM and BC are all intracellular bacteria, they are excellent targets for T cell-based vaccines. However, the sheer volume of available genomic data requires the aid of immunoinformatics for vaccine design. Using EpiMatrix, ClustiMer and EpiAssembler, a set of immunoinformatic vaccine design tools, we screened the 31 available Burkholderia genomes and performed initial tests of our selections that are candidates for an epitope-based multi-pathogen vaccine against Burkholderia species. Results Immunoinformatics analysis of 31 Burkholderia genomes yielded 350,004 9-mer candidate vaccine peptides of which 133,469 had perfect conservation across the 10 BM genomes, 175,722 had perfect conservation across the 11 BPM genomes and 40,813 had perfect conservation across the 10 BC genomes. Further screening with EpiMatrix yielded 54,010 high-scoring Class II epitopes; these were assembled into 2,880 longer highly conserved ‘immunogenic consensus sequence’ T helper epitopes. 100% of the peptides bound to at least one HLA class II allele in vitro, 92.7% bound to at least two alleles, 82.9% to three, and 75.6% of the binding results were consistent with the immunoinformatics analysis. Conclusions Our results show it is possible to rapidly identify promiscuous T helper epitopes conserved across multiple Burkholderia species and test their binding to HLA ligands in vitro. The next step in our process will be to test the epitopes ex vivo using peripheral leukocytes from BC, BPM infected humans and for immunogenicity in human HLA transgenic mice. We expect that this approach will lead to development of a licensable, pan-Burkholderia biodefense vaccine.
影响因子：
56.9
作者：
HUGHES, KT;GILLEN, KL;KARLINSEY, JE
通讯作者：
KARLINSEY, JE
开发脓毒症抗内毒素疫苗。
影响因子：
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作者：
Cross,AlanS
通讯作者：
Cross,AlanS