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

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.

近数十年来，埃博拉病毒（Ebola virus, EBOV）在非洲周期性暴发并引发人类感染，致死率极高。目前尚无可用的预防措施与治疗手段，因此迫切需要一款高效的埃博拉疫苗。本研究借助两种重组复制缺陷型黑猩猩腺病毒载体AdC7与AdC68——二者均表达2014年暴发株埃博拉病毒的糖蛋白（glycoprotein, GP）——开发了一款新型黑猩猩腺病毒载体初免-加强免疫疫苗。研究结果显示，单独使用AdC7或AdC68进行单次免疫即可激发强效的埃博拉病毒特异性抗体应答；相较于单独使用AdC7、AdC68免疫，或是采用AdC68初免-AdC7加强的免疫方案，AdC7初免-AdC68加强免疫方案在小鼠与恒河猴体内均能诱导更强效且持久的体液免疫与细胞免疫应答。该初免-加强免疫疫苗还可在生物安全二级（biosafety level 2, BSL-2）实验室环境中，保护小鼠免受埃博拉病毒样颗粒（Ebola virus-like particle, EBOVLP）的模拟感染；且经该方案免疫的恒河猴体内的抗体，可被动为机体提供针对埃博拉病毒样颗粒感染的保护作用。综上，本研究结果表明，AdC7初免-AdC68加强免疫疫苗是一款极具开发前景的候选疫苗，可用于后续对抗埃博拉病毒感染的研发工作。