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黑猩猩腺病毒载体疫苗初免-加强方案可在小鼠和恒河猴中引发针对埃博拉病毒的强烈免疫应答。

Chimpanzee adenoviral vector prime-boost regimen elicits potent immune responses against Ebola virus in mice and rhesus macaques.

机构信息

a University of Chinese Academy of Sciences , Beijing , People's Republic of China.

b Vaccine Research Center, CAS Key Laboratory of Molecular Virology and Immunology, Institut Pasteur of Shanghai, Chinese Academy of Sciences , Shanghai , People's Republic of China.

出版信息

Emerg Microbes Infect. 2019;8(1):1086-1097. doi: 10.1080/22221751.2019.1644968.

Abstract

In the last few decades, Ebola virus (EBOV) has emerged periodically and infected people in Africa, resulting in an extremely high mortality rate. With no available prophylaxis or cure so far, a highly effective Ebola vaccine is urgently needed. In this study, we developed a novel chimpanzee adenovirus-based prime-boost vaccine by exploiting two recombinant replication-deficient chimpanzee adenoviral vectors, AdC7 and AdC68, which express glycoproteins (GP) of the EBOV strain identified in the 2014 outbreak. Our results indicated that a single immunization using AdC7 or AdC68 could stimulate potent EBOV-specific antibody responses, whereas the AdC7 prime-AdC68 boost regimen induced much stronger and sustained humoral and cellular immune responses in both mice and rhesus monkeys, compared with AdC7 or AdC68 single vaccination or the AdC68 prime-AdC7 boost regimen. This prime-boost vaccine could also protect mice from the simulated infection with EBOV-like particle (EBOVLP) in biosafety level 2 (BSL-2) laboratories, and antibodies from the prime-boost immunized rhesus macaques could passively provide protection against EBOVLP infection. Altogether, our results show that the AdC7 prime-AdC68 boost vaccine is a promising candidate for further development to combat EBOV infections.

摘要

在过去的几十年中,埃博拉病毒(EBOV)周期性出现并感染了非洲的人们,导致极高的死亡率。到目前为止,还没有有效的预防或治疗方法,因此急需一种非常有效的埃博拉疫苗。在这项研究中,我们利用两种表达 2014 年暴发的 EBOV 株糖蛋白(GP)的重组复制缺陷型黑猩猩腺病毒载体 AdC7 和 AdC68,开发了一种新型的黑猩猩腺病毒基初免-加强疫苗。我们的结果表明,单次免疫 AdC7 或 AdC68 可刺激强烈的 EBOV 特异性抗体反应,而 AdC7 初免-AdC68 加强方案在小鼠和恒河猴中诱导的体液和细胞免疫反应比 AdC7 或 AdC68 单接种或 AdC68 初免-AdC7 加强方案更强且更持久。这种初免-加强疫苗还可以保护小鼠免受 BSL-2 实验室中类似埃博拉病毒粒子(EBOVLP)的模拟感染,来自初免-加强免疫的恒河猴的抗体可以被动提供针对 EBOVLP 感染的保护。总之,我们的结果表明,AdC7 初免-AdC68 加强疫苗是进一步开发用于对抗 EBOV 感染的有前途的候选疫苗。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/e6f8/6711196/563c66761c91/TEMI_A_1644968_F0001_OC.jpg

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