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首页> 外文期刊>Vaccine >Immunogenicity of sequences around HIV-1 protease cleavage sites: Potential targets and population coverage analysis for a HIV vaccine targeting protease cleavage sites
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Immunogenicity of sequences around HIV-1 protease cleavage sites: Potential targets and population coverage analysis for a HIV vaccine targeting protease cleavage sites

机译：HIV-1蛋白酶切割位点周围序列的免疫原性：靶向蛋白酶切割位点的HIV疫苗的潜在目标和人群覆盖率分析

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Developing an effective preventative vaccine against HIV-1 has proved to be a great challenge. The classical and proven vaccine approach has failed so far or produced a modest effect, new approaches are needed. In this study we evaluated the immunogenicity of the sequences around the protease cleavage sites (PCS) and the population coverage of a vaccine targeting HIV-1 PCS. The sequence conservation was evaluated by comparing entropy score of sequences around PCS with Gag and Pol. The immunogenicityof sequences around the 12 PCS (+10/-10 amino acids) was analyzed by identifying epitopes of HLA class I alleles in PCS region using four approaches: (1) identification of previously reported HLA class I allele epitopes around PCS region; (2) screening and validating epitopes of 8 HLA class I alleles common to most world populations using iTopia Epitope Discovery system and IFN-7 ELISpot assays; (3) screening of 151 patients of Pumwani cohort for PBMC IFN-7 ELISPOT responses to the subtype A and D consensus around PCS region; and (4) prediction of HLA alleles with epitopes around the PCS using NetMHCpan. Population coverage was calculated using the web-based analysis tool of the Immune Epitope Database based on HLA class I genotype frequencies from dbMHC database. The results showed that many HLA class I alleles have multiple epitopes in the 12 PCS regions, indicating sequence immunogenicity around PCS. Multiple epitopes of many HLA class I alleles common to >95% world populations have been identifiedaround the 12 PCS region. Targeting these sites is a feasible vaccine approach.
机译：开发一种有效的针对HIV-1的预防性疫苗已被证明是一个巨大的挑战。迄今为止，经典且经过验证的疫苗方法已经失败或产生了适度的效果，需要新的方法。在这项研究中，我们评估了蛋白酶切割位点（PCS）周围序列的免疫原性以及针对HIV-1 PCS的疫苗的人群覆盖率。通过比较PCS周围序列与Gag和Pol的熵得分来评估序列保守性。通过使用四种方法鉴定PCS区域中的HLA I类等位基因表位来分析12个PCS（+ 10 / -10个氨基酸）周围的序列的免疫原性：（1）鉴定先前报道的PCS区域附近的HLA I类等位基因表位; （2）使用iTopia表位发现系统和IFN-7 ELISpot分析法筛选和验证大多数世界人口共有的8个HLA I类等位基因表位; （3）筛选151例Pumwani队列患者对PCS区域周围A和D亚型共有的PBMC IFN-7 ELISPOT反应; （4）使用NetMHCpan预测PCS周围具有表位的HLA等位基因。使用基于dbMHC数据库的HLA I类基因型频率的免疫表位数据库的基于网络的分析工具，计算了人口覆盖率。结果表明，许多HLA I类等位基因在12个PCS区域具有多个表位，表明PCS周围具有序列免疫原性。在12个PCS区域附近，已经确定了世界上> 95％的人口共有的许多HLA I类等位基因的多个表位。针对这些部位是可行的疫苗方法。

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