Division of Immunology, Queensland Institute of Medical Research, The Bancroft Centre, 300 Herston Road, P.O. Royal Brisbane Hospital, Brisbane, QLD 4029, Australia.
Int J Parasitol. 2011 Jan;41(1):3-20. doi: 10.1016/j.ijpara.2010.08.002. Epub 2010 Sep 16.
The Plasmodium parasite, the causative agent of malaria, is an excellent model for immunomic-based approaches to vaccine development. The Plasmodium parasite has a complex life cycle with multiple stages and stage-specific expression of ∼5300 putative proteins. No malaria vaccine has yet been licensed. Many believe that an effective vaccine will need to target several antigens and multiple stages, and will require the generation of both antibody and cellular immune responses. Vaccine efforts to date have been stage-specific and based on only a very limited number of proteins representing <0.5% of the genome. The recent availability of comprehensive genomic, proteomic and transcriptomic datasets from human and selected non-human primate and rodent malarias provide a foundation to exploit for vaccine development. This information can be mined to identify promising vaccine candidate antigens, by proteome-wide screening of antibody and T cell reactivity using specimens from individuals exposed to malaria and technology platforms such as protein arrays, high throughput protein production and epitope prediction algorithms. Such antigens could be incorporated into a rational vaccine development process that targets specific stages of the Plasmodium parasite life cycle with immune responses implicated in parasite elimination and control. Immunomic approaches which enable the selection of the best possible targets by prioritising antigens according to clinically relevant criteria may overcome the problem of poorly immunogenic, poorly protective vaccines that has plagued malaria vaccine developers for the past 25 years. Herein, current progress and perspectives regarding Plasmodium immunomics are reviewed.
疟原虫寄生虫是疟疾的病原体,是基于免疫组学的疫苗开发方法的绝佳模型。疟原虫寄生虫具有复杂的生命周期,有多个阶段和阶段特异性表达的约 5300 种假定蛋白质。目前还没有批准任何疟疾疫苗。许多人认为,有效的疫苗将需要针对几种抗原和多个阶段,并需要产生抗体和细胞免疫反应。迄今为止,疫苗接种工作是针对特定阶段的,并且仅基于代表基因组 <0.5%的非常有限数量的蛋白质。人类和选定的非人类灵长类动物和啮齿动物疟疾的综合基因组、蛋白质组和转录组数据集的最近可用性为疫苗开发提供了一个基础。可以通过使用暴露于疟疾的个体的标本和技术平台(例如蛋白质阵列、高通量蛋白质生产和表位预测算法)进行抗体和 T 细胞反应的全蛋白质组筛选,从这些信息中挖掘出有前途的疫苗候选抗原。这些抗原可以被纳入一个合理的疫苗开发过程中,该过程针对疟原虫寄生虫生命周期的特定阶段,免疫反应与寄生虫的消除和控制有关。免疫组学方法可以根据临床相关标准对抗原进行优先级排序,从而选择最佳的可能目标,这可能克服过去 25 年来困扰疟疾疫苗开发者的免疫原性差、保护效果差的疫苗问题。本文综述了疟原虫免疫组学的当前进展和展望。