Proietti Carla, Doolan Denise L
Infectious Diseases Program, QIMR Berghofer Medical Research Institute Brisbane, QLD, Australia.
Front Microbiol. 2015 Jan 22;5:741. doi: 10.3389/fmicb.2014.00741. eCollection 2014.
Historically, vaccines have been designed to mimic the immunity induced by natural exposure to the target pathogen, but this approach has not been effective for any parasitic pathogen of humans or complex pathogens that cause chronic disease in humans, such as Plasmodium. Despite intense efforts by many laboratories around the world on different aspects of Plasmodium spp. molecular and cell biology, epidemiology and immunology, progress towards the goal of an effective malaria vaccine has been disappointing. The premise of rational vaccine design is to induce the desired immune response against the key pathogen antigens or epitopes targeted by protective immune responses. We advocate that development of an optimally efficacious malaria vaccine will need to improve on nature, and that this can be accomplished by rational vaccine design facilitated by mining genomic, proteomic and transcriptomic datasets in the context of relevant biological function. In our opinion, modern genome-based rational vaccine design offers enormous potential above and beyond that of whole-organism vaccines approaches established over 200 years ago where immunity is likely suboptimal due to the many genetic and immunological host-parasite adaptations evolved to allow the Plasmodium parasite to coexist in the human host, and which are associated with logistic and regulatory hurdles for production and delivery.
从历史上看，疫苗的设计旨在模拟自然接触目标病原体所诱导的免疫反应，但这种方法对人类的任何寄生性病原体或导致人类慢性疾病的复杂病原体（如疟原虫）均无效。尽管世界各地许多实验室在疟原虫属的分子和细胞生物学、流行病学及免疫学等不同方面付出了巨大努力，但在研发有效疟疾疫苗这一目标上所取得的进展却令人失望。合理疫苗设计的前提是针对保护性免疫反应所靶向的关键病原体抗原或表位诱导出所需的免疫反应。我们主张，要研发出最优效的疟疾疫苗需要超越自然状态进行改进，而这可以通过在相关生物学功能背景下挖掘基因组、蛋白质组和转录组数据集来推动合理疫苗设计来实现。我们认为，基于现代基因组的合理疫苗设计具有巨大潜力，远超200多年前建立的全生物体疫苗方法，因为由于疟原虫寄生虫与人类宿主共同进化出的许多遗传和免疫宿主-寄生虫适应性，全生物体疫苗的免疫效果可能欠佳，而且这些适应性与生产和交付过程中的后勤及监管障碍相关。
