Lew-Tabor A E, Rodriguez Valle M
The University of Queensland, Centre for Animal Science, Queensland Alliance for Agriculture and Food Innovation, Carmody Rd., St. Lucia 4072, QLD, Australia; Murdoch University, Centre for Comparative Genomics, Murdoch 6150, WA, Australia.
The University of Queensland, Centre for Animal Science, Queensland Alliance for Agriculture and Food Innovation, Carmody Rd., St. Lucia 4072, QLD, Australia.
Ticks Tick Borne Dis. 2016 Jun;7(4):573-85. doi: 10.1016/j.ttbdis.2015.12.012. Epub 2015 Dec 18.
The field of reverse vaccinology developed as an outcome of the genome sequence revolution. Following the introduction of live vaccinations in the western world by Edward Jenner in 1798 and the coining of the phrase 'vaccine', in 1881 Pasteur developed a rational design for vaccines. Pasteur proposed that in order to make a vaccine that one should 'isolate, inactivate and inject the microorganism' and these basic rules of vaccinology were largely followed for the next 100 years leading to the elimination of several highly infectious diseases. However, new technologies were needed to conquer many pathogens which could not be eliminated using these traditional technologies. Thus increasingly, computers were used to mine genome sequences to rationally design recombinant vaccines. Several vaccines for bacterial and viral diseases (i.e. meningococcus and HIV) have been developed, however the on-going challenge for parasite vaccines has been due to their comparatively larger genomes. Understanding the immune response is important in reverse vaccinology studies as this knowledge will influence how the genome mining is to be conducted. Vaccine candidates for anaplasmosis, cowdriosis, theileriosis, leishmaniasis, malaria, schistosomiasis, and the cattle tick have been identified using reverse vaccinology approaches. Some challenges for parasite vaccine development include the ability to address antigenic variability as well the understanding of the complex interplay between antibody, mucosal and/or T cell immune responses. To understand the complex parasite interactions with the livestock host, there is the limitation where algorithms for epitope mining using the human genome cannot directly be adapted for bovine, for example the prediction of peptide binding to major histocompatibility complex motifs. As the number of genomes for both hosts and parasites increase, the development of new algorithms for pan-genomic mining will continue to impact the future of parasite and ricketsial (and other tick borne pathogens) disease vaccine development.
反向疫苗学领域是基因组序列革命的产物。1798年爱德华·詹纳在西方世界引入活疫苗并创造了“疫苗”一词后，1881年巴斯德提出了一种合理的疫苗设计方法。巴斯德提出，为了制造一种疫苗，应该“分离、灭活并注射微生物”，在接下来的100年里，疫苗学的这些基本规则在很大程度上得到了遵循，从而消灭了几种高度传染性疾病。然而，需要新技术来攻克许多无法用这些传统技术消灭的病原体。因此，越来越多地使用计算机挖掘基因组序列来合理设计重组疫苗。已经开发出了几种针对细菌和病毒疾病（如脑膜炎球菌和艾滋病毒）的疫苗，然而，寄生虫疫苗面临的持续挑战在于其基因组相对较大。在反向疫苗学研究中，了解免疫反应很重要，因为这一知识将影响基因组挖掘的方式。已经使用反向疫苗学方法鉴定出了无形体病、牛巴贝斯虫病、泰勒虫病、利什曼病、疟疾、血吸虫病和牛蜱的候选疫苗。寄生虫疫苗开发面临的一些挑战包括应对抗原变异性的能力以及对抗体、黏膜和/或T细胞免疫反应之间复杂相互作用的理解。为了理解寄生虫与家畜宿主之间的复杂相互作用，存在一个局限性，即使用人类基因组进行表位挖掘的算法不能直接适用于牛，例如预测肽与主要组织相容性复合体基序的结合。随着宿主和寄生虫基因组数量的增加，用于泛基因组挖掘的新算法的开发将继续影响寄生虫和立克次体（以及其他蜱传病原体）疾病疫苗开发的未来。
