Recombinant proteins of Zaire ebolavirus induce potent humoral and cellular immune responses and protect against live virus infection in mice.
Recombinant proteins of Zaire ebolavirus induce potent humoral and cellular immune responses and protect against live virus infection in mice.
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DOI：
10.1016/j.vaccine.2017.01.068
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发表时间：
2018-05-24
期刊：
影响因子：
5.5
通讯作者：
Dye JM
中科院分区：
文献类型：
--
作者：
Lehrer AT;Wong TS;Lieberman MM;Humphreys T;Clements DE;Bakken RR;Hart MK;Pratt WD;Dye JM
人类感染丝状病毒是剧毒的，可引起出血热，死亡率高达90%。除了自然感染外，利用这些病毒作为生物恐怖主义武器的能力也令人严重关切。目前，还没有获得许可的疫苗或治疗方法来对抗这些感染。疾病的发病机制涉及宿主免疫系统的失调，导致先天和适应性免疫反应受损，随后发展为淋巴细胞减少、血小板减少、出血和死亡。关于少数感染幸存者的问题仍然存在，他们设法建立有效的适应性免疫反应。这些问题涉及这种反应的体液和细胞成分，以及这种反应是否可以通过适当的预防性疫苗引起。本文报道的数据描述了一种重组亚基埃博拉病毒候选疫苗的生产和评价，该候选疫苗由表达扎伊尔埃博拉病毒（EBOV）表面糖蛋白（GP）和基质蛋白VP24和VP40组成。重组亚基蛋白在小鼠中显示出高度免疫原性，产生体液和细胞反应，并且非常有效，可提供高达100%的保护，抵御活病毒的致命攻击。这些结果在EBOV小鼠模型中证明了这种重组非复制候选疫苗的概念，这有助于阐明保护的免疫相关关系，值得进一步开发。
Infections with filoviruses in humans are highly virulent, causing hemorrhagic fevers which result in up to 90% mortality. In addition to natural infections, the ability to use these viruses as bioterrorist weapons is of significant concern. Currently, there are no licensed vaccines or therapeutics available to combat these infections. The pathogenesis of disease involves the dysregulation of the host’s immune system, which results in impairment of the innate and adaptive immune responses, with subsequent development of lymphopenia, thrombocytopenia, hemorrhage, and death. Questions remain with regard to the few survivors of infection, who manage to mount an effective adaptive immune response. These questions concern the humoral and cellular components of this response, and whether such a response can be elicited by an appropriate prophylactic vaccine. The data reported herein describe the production and evaluation of a recombinant subunit Ebola virus vaccine candidate consisting of insect cell expressed Zaire ebolavirus (EBOV) surface glycoprotein (GP) and the matrix proteins VP24 and VP40. The recombinant subunit proteins are shown to be highly immunogenic in mice, yielding both humoral and cellular responses, as well as highly efficacious, providing up to 100% protection against a lethal challenge with live virus. These results demonstrate proof of concept for such a recombinant non-replicating vaccine candidate in the mouse model of EBOV which helps to elucidate immune correlates of protection and warrants further development.
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5.5
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