EpiVax, Inc., Providence, Rhode Island, United States.
Vaccine. 2012 Dec 14;30(52):7547-60. doi: 10.1016/j.vaccine.2012.10.042. Epub 2012 Oct 24.
HIV genomic sequence variability has complicated efforts to generate an effective globally relevant vaccine. Regions of the viral genome conserved in sequence and across time may represent the "Achilles' heel" of HIV. In this study, highly conserved T-cell epitopes were selected using immunoinformatics tools combining HLA-A2 supertype binding predictions with relative global conservation. Analysis performed in 2002 on 10,803 HIV-1 sequences, and again in 2009, on 43,822 sequences, yielded 38 HLA-A2 epitopes. These epitopes were experimentally validated for HLA binding and immunogenicity with PBMCs from HIV-infected patients in Providence, Rhode Island, and/or Bamako, Mali. Thirty-five (92%) stimulated an IFNγ response in PBMCs from at least one subject. Eleven of fourteen peptides (79%) were confirmed as HLA-A2 epitopes in both locations. Validation of these HLA-A2 epitopes conserved across time, clades, and geography supports the hypothesis that such epitopes could provide effective coverage of virus diversity and would be appropriate for inclusion in a globally relevant HIV vaccine.
HIV 基因组序列的变异性使得生成有效的全球相关疫苗的努力变得复杂。在序列和时间上保守的病毒基因组区域可能代表 HIV 的“阿喀琉斯之踵”。在这项研究中，使用免疫信息学工具选择了高度保守的 T 细胞表位，该工具结合了 HLA-A2 超型结合预测和相对全球保守性。2002 年对 10803 个 HIV-1 序列进行了分析，2009 年再次对 43822 个序列进行了分析，得到了 38 个 HLA-A2 表位。这些表位使用来自罗得岛州普罗维登斯和/或马里巴马科的 HIV 感染患者的 PBMC 进行了 HLA 结合和免疫原性的实验验证。至少有一个受试者的 PBMC 中 35 个（92%）刺激了 IFNγ 反应。在两个地点都确认了 14 个肽中的 11 个（79%）为 HLA-A2 表位。这些在时间、谱系和地理上保守的 HLA-A2 表位的验证支持这样的假设，即这些表位可以有效地覆盖病毒多样性，并且适合包含在具有全球相关性的 HIV 疫苗中。
