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血液期疟疾疫苗:用于鉴定新型候选疫苗的基因组后策略

Blood-stage malaria vaccines: post-genome strategies for the identification of novel vaccine candidates.

作者信息

Ntege Edward H, Takashima Eizo, Morita Masayuki, Nagaoka Hikaru, Ishino Tomoko, Tsuboi Takafumi

机构信息

a Division of Malaria Research , Proteo-Science Center, Ehime University , Matsuyama , Ehime , Japan.

b Division of Molecular Parasitology , Proteo-Science Center, Ehime University , Toon , Ehime , Japan.

出版信息

Expert Rev Vaccines. 2017 Aug;16(8):769-779. doi: 10.1080/14760584.2017.1341317. Epub 2017 Jun 19.

DOI:10.1080/14760584.2017.1341317
PMID:28604122
Abstract

An efficacious malaria vaccine is necessary to advance the current control measures towards malaria elimination. To-date, only RTS,S/AS01, a leading pre-erythrocytic stage vaccine completed phase 3 trials, but with an efficacy of 28-36% in children, and 18-26% in infants, that waned over time. Blood-stage malaria vaccines protect against disease, and are considered effective targets for the logical design of next generation vaccines to improve the RTS,S field efficacy. Therefore, novel blood-stage vaccine candidate discovery efforts are critical, albeit with several challenges including, high polymorphisms in vaccine antigens, poor understanding of targets of naturally protective immunity, and difficulties in the expression of high AT-rich plasmodial proteins. Areas covered: PubMed ( www.ncbi.nlm.nih.gov/pubmed ) was searched to review the progress and future prospects of malaria vaccine research and development. We focused on post-genome vaccine candidate discovery, malaria vaccine development, sequence diversity, pre-clinical and clinical trials. Expert commentary: Post-genome high-throughput technologies using wheat germ cell-free protein synthesis technology and immuno-profiling with sera from malaria patients with clearly defined outcomes are highlighted to overcome current challenges of malaria vaccine candidate discovery.

摘要

一种有效的疟疾疫苗对于推动当前疟疾控制措施向消除疟疾迈进至关重要。迄今为止,只有领先的红细胞前期疫苗RTS,S/AS01完成了3期试验,但其在儿童中的疗效为28%-36%,在婴儿中的疗效为18%-26%,且随着时间推移疗效会下降。血液期疟疾疫苗可预防疾病,被认为是合理设计下一代疫苗以提高RTS,S现场疗效的有效靶点。因此,尽管存在包括疫苗抗原高度多态性、对天然保护性免疫靶点了解不足以及富含AT的疟原虫蛋白表达困难等若干挑战,但新型血液期疫苗候选物的发现工作仍至关重要。涵盖领域:检索了PubMed(www.ncbi.nlm.nih.gov/pubmed)以综述疟疾疫苗研发的进展和未来前景。我们重点关注了后基因组疫苗候选物发现、疟疾疫苗开发、序列多样性、临床前和临床试验。专家评论:强调了利用小麦胚无细胞蛋白质合成技术的后基因组高通量技术以及对结局明确的疟疾患者血清进行免疫分析,以克服当前疟疾疫苗候选物发现面临的挑战。

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