Koita O A, Dabitao D, Mahamadou I, Tall M, Dao S, Tounkara A, Guiteye H, Noumsi C, Thiero O, Kone M, Rivera D, McMurry J A, Martin W, De Groot A S
Applied Molecular Biology Laboratory, Faculté de Sciences et Technologie, University of Mali, Bamako, Mali.
Hum Vaccin. 2006 May-Jun;2(3):119-28. doi: 10.4161/hv.2869. Epub 2006 May 25.
The design of epitope-driven vaccines for HIV has been significantly hampered by concerns about conservation of vaccine epitopes across clades of HIV. In previous work, we have described a computer-driven method for a cross-clade HIV vaccine comprised of overlapping, highly conserved helper T-cell epitopes or "immunogenic consensus sequence epitopes" (ICS epitopes). Here, we evaluated and compared the immunogenicity of 20 ICS HIV epitopes in ELISpot assays performed using peripheral blood monocytes (PBMC) from HIV-infected donors in Providence, Rhode Island, USA and in Bamako, Mali, West Africa. Each core 9-mer HIV sequence contained in a given consensus peptide was conserved in at least 105 to as many as 2,250 individual HIV-1 strains. Nineteen of the 20 ICS epitopes (95%) were confirmed in ELISpot assays using PBMC obtained from 13 healthy, HIV-1 infected subjects in Providence, and thirteen of the epitopes (65%) were confirmed in ELISpot assays using PBMC derived from 42 discarded blood units obtained at the Central Blood Bank in Bamako. Twelve of the epitopes were confirmed in ELISpot assays performed both in Providence and Bamako. These data confirm the utility of bioinformatics tools to select and design novel vaccines containing "immunogenic consensus sequence" T-cell epitopes for a globally relevant vaccine against HIV; a similar approach may also be useful for any pathogen that exhibits high variability (influenza, HCV, or variola for example). An HIV vaccine containing these immunogenic consensus sequences is currently under development.
由于担心HIV不同进化枝间疫苗表位的保守性，HIV表位驱动疫苗的设计受到了显著阻碍。在之前的工作中，我们描述了一种计算机驱动的方法，用于设计一种由重叠的、高度保守的辅助性T细胞表位或“免疫原性共有序列表位”（ICS表位）组成的跨进化枝HIV疫苗。在此，我们在美国罗德岛州普罗维登斯市和西非马里巴马科市，使用来自HIV感染供体的外周血单核细胞（PBMC）进行ELISpot分析，评估并比较了20个ICS HIV表位的免疫原性。给定共有肽中包含的每个核心9聚体HIV序列，在至少105个至多达2250个个体HIV-1毒株中是保守的。在使用从普罗维登斯市13名健康的HIV-1感染受试者获得的PBMC进行的ELISpot分析中，20个ICS表位中的19个（95%）得到了证实；在使用从巴马科中央血库获得的42份废弃血样中提取的PBMC进行的ELISpot分析中，13个表位（65%）得到了证实。其中12个表位在普罗维登斯市和巴马科市进行的ELISpot分析中均得到了证实。这些数据证实了生物信息学工具在选择和设计含有“免疫原性共有序列”T细胞表位的新型疫苗方面的实用性，这种疫苗可用于全球范围内针对HIV的相关疫苗；类似的方法可能对任何具有高变异性的病原体（例如流感、HCV或天花）也有用。一种含有这些免疫原性共有序列的HIV疫苗目前正在研发中。
