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A heterologous prime-boost Ebola virus vaccine regimen induces durable neutralizing antibody response and prevents Ebola virus-like particle entry in mice
Antiviral Research ( IF 4.5 ) Pub Date : 2017-07-18 , DOI: 10.1016/j.antiviral.2017.07.009
Tan Chen , Dapeng Li , Yufeng Song , Xi Yang , Qingwei Liu , Xia Jin , Dongming Zhou , Zhong Huang

Ebola virus (EBOV) is one of the most virulent pathogens known to humans. Neutralizing antibodies play a major role in the protection against EBOV infections. Thus, an EBOV vaccine capable of inducing a long-lasting neutralizing antibody response is highly desirable. We report here that a heterologous prime-boost vaccine regimen can elicit durable EBOV-neutralizing antibody response in mice. A chimpanzee serotype 7 adenovirus expressing EBOV GP (denoted AdC7-GP) was generated and used for priming. A truncated version of EBOV GP1 protein (denoted GP1t) was produced at high levels in Drosophila S2 cells and used for boosting. Mouse immunization studies showed that the AdC7-GP prime/GP1t boost vaccine regimen was more potent in eliciting neutralizing antibodies than either the AdC7-GP or GP1t alone. Neutralizing antibodies induced by the heterologous prime-boost regimen sustained at high titers for at least 18 weeks after immunization. Significantly, in vivo challenge studies revealed that the entry of reporter EBOV-like particles was efficiently blocked in mice receiving the heterologous prime-boost regimen even at 18 weeks after the final dose of immunization. These results suggest that this novel AdC7-GP prime/GP1t boost regimen represents an EBOV vaccine approach capable of establishing long-term protection, and therefore warrants further development.



中文翻译:

异源初免-加强型埃博拉病毒疫苗方案可诱导持久的中和抗体反应并防止埃博拉病毒样颗粒进入小鼠

埃博拉病毒(EBOV)是人类已知的最强毒的病原体之一。中和抗体在针对EBOV感染的保护中起主要作用。因此,非常需要能够诱导持久的中和抗体应答的EBOV疫苗。我们在这里报告,异源的初免-加强疫苗方案可以在小鼠中引起持久的EBOV中和抗体反应。产生了表达EBOV GP的黑猩猩血清型7腺病毒(表示为AdC7-GP),并用于引发。果蝇大量生产了截短形式的EBOV GP1蛋白(称为GP1t)S2细胞,用于加强免疫力。小鼠免疫研究表明,与单独使用AdC7-GP或GP1t相比,AdC7-GP初免/ GP1t加强疫苗方案在诱发中和抗体方面更有效。免疫后,异源初免-加强疗法诱导的中和抗体在高滴度下持续至少18周。重要的是,体内攻击研究表明,即使在最终免疫接种后的第18周,接受异源初免-加强疗法的小鼠中,记者EBOV样颗粒的进入也被有效地阻断了。这些结果表明,这种新颖的AdC7-GP初免/ GP1t加强方案代表了能够建立长期保护的EBOV疫苗方法,因此值得进一步开发。

更新日期:2017-07-18
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