Designing malaria vaccines to circumvent antigen variability.
Designing malaria vaccines to circumvent antigen variability.
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DOI：
10.1016/j.vaccine.2015.09.110
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发表时间：
2015-12-22
期刊：
影响因子：
5.5
通讯作者：
Plowe CV
中科院分区：
文献类型：
--
作者：
Ouattara A;Barry AE;Dutta S;Remarque EJ;Beeson JG;Plowe CV
有效的疫苗将大大增强根除疟疾的前景，但寄生虫遗传多样性对疟疾疫苗的功效构成了主要障碍。在最近的临床前和现场试验中，基于多态性恶性疟原虫抗原的疫苗仅对同源菌株有效，这引发了对等位基因特异性免疫的担忧，例如困扰流感和艾滋病毒疫苗的等位基因特异性免疫。最先进的疟疾疫苗 RTS,S 针对恶性疟原虫环子孢子蛋白上相对保守的表位。经过 40 多年的开发和测试，RTS,S 在 2 期和 3 期试验中显示出对临床疟疾显着但有限的功效。正在进行的辐照子孢子疫苗的第二阶段研究将确定高剂量全生物体疫苗所赋予的针对同源实验性疟疾攻击的全面保护是否可以在现场提供针对多种菌株的保护。在这里，我们回顾和评估了设计广泛交叉保护性疟疾疫苗所采取的方法。
Prospects for malaria eradication will be greatly enhanced by an effective vaccine, but parasite genetic diversity poses a major impediment to malaria vaccine efficacy. In recent pre-clinical and field trials, vaccines based on polymorphic Plasmodium falciparum antigens have shown efficacy only against homologous strains, raising the specter of allele-specific immunity such as that which plagues vaccines against influenza and HIV. The most advanced malaria vaccine, RTS,S, targets relatively conserved epitopes on the P. falciparum circumsporozoite protein. After more than 40 years of development and testing, RTS,S, has shown significant but modest efficacy against clinical malaria in phase 2 and 3 trials. Ongoing phase 2 studies of an irradiated sporozoite vaccine will ascertain whether the full protection against homologous experimental malaria challenge conferred by high doses of a whole organism vaccine can provide protection against diverse strains in the field. Here we review and evaluate approaches being taken to design broadly cross-protective malaria vaccines.