PDF(Sci-hub)
Abstract：
A licensed vaccine against Ebola virus (EBOV) remains unavailable, despite >11 000 deaths from the 2014-2016 outbreak of EBOV disease in West Africa. Past studies have shown that recombinant vaccine viruses expressing EBOV glycoprotein (GP) are able to protect nonhuman primates (NHPs) from a lethal EBOV challenge. However, these vaccines express the viral GP-based EBOV variants found in Central Africa, which has 97.3% amino acid homology to the Makona variant found in West Africa. Our previous study showed that a recombinant adenovirus serotype 5 (Ad5)-vectored vaccine expressing the Makona EBOV GP (MakGP) was safe and immunogenic during clinical trials in China, but it is unknown whether the vaccine protects against EBOV infection. Here, we demonstrate that guinea pigs immunized with Ad5-MakGP developed robust humoral responses and were protected against exposure to guinea pig-adapted EBOV. Ad5-MakGP also elicited specific B- and T-cell immunity in NHPs and conferred 100% protection when animals were challenged 4 weeks after immunization. These results support further clinical development of this candidate and highlight the utility of Ad5-MakGP as a prophylactic measure in future outbreaks of EBOV disease.
摘要：
针对埃博拉病毒（EBOV）的许可疫苗仍然不可用，尽管西非2014-2016年爆发的EBOV病导致超过11,000人死亡。过去的研究表明，表达EBOV糖蛋白（GP）的重组疫苗病毒能够保护非人灵长类动物（NHP）免受致命的EBOV攻击。然而,这些疫苗表达了在中非发现的基于GP的EBOV病毒变体，与西非发现的Makona变体具有97.3％的氨基酸同源性。我们先前的研究表明，在中国的临床试验中，表达MakonaEBOVGP（MakGP）的重组腺病毒血清型5（Ad5）载体疫苗是安全且具有免疫原性的。但目前尚不清楚该疫苗是否能预防EBOV感染。这里,我们证明，用Ad5-MakGP免疫的豚鼠产生了强烈的体液反应，并且可以防止暴露于豚鼠适应的EBOV。Ad5-MakGP还在NHP中引发特异性B-和T-细胞免疫,并且在免疫后4周攻击动物时赋予100%保护。这些结果支持了该候选物的进一步临床开发，并强调了Ad5-MakGP在未来EBOV疾病爆发中作为预防措施的实用性。
