De Groot Anne S, Martin William
TB/HIV Research Laboratory, Brown University, International Health Institute, Box GB473, Providence, RI 02912, USA.
Novartis Found Symp. 2003;254:57-72; discussion 72-6, 98-101, 250-2.
Since the publication of the complete genome of a pathogenic bacterium in 1995, more than 50 bacterial pathogens have been sequenced and at least 120 additional projects are currently underway. Faced with the expanding volume of information now available from genome databases, vaccinologists are turning to epitope mapping tools to screen vaccine candidates. Bioinformatics tools such as EpiMatrix and Conservatrix, which search for unique or multi-HLA-restricted (promiscuous) T cell epitopes and can find epitopes that are conserved across variant strains of the same pathogen, have accelerated the process of epitope mapping. Additional tools for screening epitopes for similarity to 'self' (BlastiMer) and for assembling putative epitopes into strings if they overlap (EpiAssembler) have been developed at EpiVax. Tools that map proteasome cleavage sires are available on the Internet. When used together, these bioinformatics tools offer a significant advantage over traditional methods of vaccine design since high throughput screening and design is performed in silico, followed by confirmatory studies in vitro. These new tools are being used to develop novel vaccines and therapeutics for the prevention and treatment of infectious diseases such as HIV, hepatitis C, tuberculosis, and some cancers. More recent applications of the tools involve deriving novel vaccine candidates directly from whole genomes, an approach that has been named 'genome to vaccine'.
自1995年一种致病细菌的完整基因组公布以来，已有50多种细菌病原体被测序，目前至少还有120个项目正在进行。面对基因组数据库中现有的信息量不断增加，疫苗学家正在转向表位作图工具来筛选候选疫苗。诸如EpiMatrix和Conservatrix等生物信息学工具，可搜索独特的或多HLA限制（混杂）的T细胞表位，并能找到在同一病原体的不同菌株中保守的表位，加速了表位作图的进程。EpiVax开发了其他用于筛选与“自身”相似性的表位（BlastiMer）以及如果表位重叠则将推定表位组装成串的工具（EpiAssembler）。在互联网上可以找到绘制蛋白酶体切割位点的工具。这些生物信息学工具一起使用时，与传统疫苗设计方法相比具有显著优势，因为高通量筛选和设计是在计算机上进行的，随后进行体外验证研究。这些新工具正被用于开发用于预防和治疗诸如艾滋病毒、丙型肝炎、结核病和某些癌症等传染病的新型疫苗和疗法。这些工具的最新应用包括直接从全基因组中推导新型候选疫苗，这种方法被称为“从基因组到疫苗”。
