Malaria vaccines and human immune responses.
Malaria vaccines and human immune responses.
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DOI：
10.1016/j.mib.2016.04.006
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发表时间：
2016-08
影响因子：
5.4
通讯作者：
Zavala F
中科院分区：
文献类型：
--
作者：
Long CA;Zavala F
RTS，S疫苗在儿童中的有效性支持了疟疾疫苗的概念。RTS，S疫苗的有效性有限，寿命短，因此需要改进。无性阶段疫苗试验令人失望; TBV尚处于早期阶段，应寻求保护性免疫的抗原组合和标志物，对性阶段和病媒的研究可提供减少传播的新方法。在过去十年中，仍然非常需要更有效的工具来防治这一严重的全球性疾病。针对恶性疟原虫环子孢子蛋白的RTS，S III期试验的积极结果表明，疟疾疫苗可以为流行地区的儿童提供部分保护，但其有限的效力和相对较短的保护窗口要求必须寻求新一代更有效的疫苗。有证据表明，抗寄生虫免疫反应也可以控制其他阶段的感染，但将这些实验结果转化为血液阶段的疫苗一直令人失望，测试传播阻断疫苗的临床努力才刚刚开始。困难包括生物体的生物学复杂性，具有大量的阶段特异性基因，其中许多在红细胞阶段是抗原多样性的。此外，似乎有必要引起高和持久的抗体滴度，解决裂殖子入侵的冗余途径，并仍然寻求保护性免疫的替代标志物。大多数疫苗研究都集中在具有明显功能作用的单一或少数抗原上，但这可能限制性太大，广泛、多抗原、多阶段的疫苗需要进一步研究。最后，涉及寄生虫性阶段和蚊子媒介的新工具和生物学见解将为减少或阻断疟疾传播提供新的途径。
HighlightsEfficacy of RTS, S vaccine in children supports the concept of a malaria vaccine.RTS, S efficacy is limited and life-span is short so improvements are necessary.Asexual stage vaccine trials have been disappointing; TBV are in early stages.Antigen combinations and markers of protective immunity should be sought.Studies of sexual stages and vectors may provide new ways to reduce transmission.Despite reductions in malaria episodes and deaths over the past decade, there is still significant need for more effective tools to combat this serious global disease. The positive results with the Phase III trial of RTS, S directed to the circumsporozoite protein of Plasmodium falciparum have established that a vaccine against malaria can provide partial protection to children in endemic areas, but its limited efficacy and relatively short window of protection mandate that new generations of more efficacious vaccines must be sought. Evidence shows that anti-parasite immune responses can control infection against other stages as well, but translating these experimental findings into vaccines for blood stages has been disappointing and clinical efforts to test a transmission blocking vaccine are just beginning. Difficulties include the biological complexity of the organism with a large array of stage-specific genes many of which in the erythrocytic stages are antigenically diverse. In addition, it appears necessary to elicit high and long-lasting antibody titers, address the redundant pathways of merozoite invasion, and still seek surrogate markers of protective immunity. Most vaccine studies have focused on a single or a few antigens with an apparent functional role, but this is likely to be too restrictive, and broad, multi-antigen, multi-stage vaccines need further investigation. Finally, novel tools and biological insights involving parasite sexual stages and the mosquito vector will provide new avenues for reducing or blocking malaria transmission.