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

机译:黑猩猩腺病毒载体初免-加强方案在小鼠和恒河猴中引发针对埃博拉病毒的强力免疫反应

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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.
机译:在过去的几十年中,埃博拉病毒(EBOV)定期出现并感染了非洲的人们,从而导致极高的死亡率。到目前为止,尚无可用的预防或治疗方法,因此迫切需要高效的埃博拉疫苗。在这项研究中,我们通过利用两个重组复制缺陷型黑猩猩腺病毒载体AdC7和AdC68开发了一种新型的基于黑猩猩腺病毒的初免-加强疫苗,它们表达了2014年爆发的EBOV株的糖蛋白(GP)。我们的结果表明,与AdC7或AdC68相比,使用AdC7或AdC68进行的单次免疫可以刺激有效的EBOV特异性抗体应答,而AdC7初次AdC68增强方案在小鼠和恒河猴中诱导出更强的持续体液和细胞免疫应答。单次疫苗接种或AdC68初免-AdC7加强方案。这种初免-加强疫苗还可以保护小鼠免受生物安全等级2(BSL-2)实验室中EBOV样颗粒(EBOVLP)的模拟感染,并且初免-加强免疫恒河猴的抗体可以被动地提供针对EBOVLP感染的保护。总之,我们的结果表明,AdC7初免-AdC68加强疫苗是抗击EBOV感染的进一步开发的有希望的候选者。

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