Chimpanzee adenovirus vaccine generates acute and durable protective immunity against ebolavirus challenge
Chimpanzee adenovirus vaccine generates acute and durable protective immunity against ebolavirus challenge
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DOI：
10.1038/nm.3702
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发表时间：
2014-10-01
期刊：
影响因子：
82.9
通讯作者：
Sullivan, Nancy J.
中科院分区：
文献类型：
--
作者：
Stanley, Daphne A.;Honko, Anna N.;Sullivan, Nancy J.
埃博拉病毒病导致高死亡率，目前的疫情在西非蔓延势头不减。编码埃博拉病毒糖蛋白（GP）的人5型腺病毒载体（rAd5）在猕猴中产生针对急性致死性扎伊尔埃博拉病毒（EBOV）攻击的保护性免疫，但未能保护对Ad5免疫的动物，这表明自然Ad5暴露可能限制疫苗在人类中的效力。在这里，我们表明，黑猩猩衍生的复制缺陷型腺病毒（ChAd）疫苗也迅速诱导一致的保护，对急性致死性EBOV的挑战猕猴。由于保护作用在几个月内减弱，我们用修饰的安卡拉牛痘（MVA）加强了ChAd3，并首次产生了针对致命EBOV攻击的持久保护。
Ebolavirus disease causes high mortality, and the current outbreak has spread unabated through West Africa. Human adenovirus type 5 vectors (rAd5) encoding ebolavirus glycoprotein (GP) generate protective immunity against acute lethal Zaire ebolavirus (EBOV) challenge in macaques, but fail to protect animals immune to Ad5, suggesting natural Ad5 exposure may limit vaccine efficacy in humans. Here we show that a chimpanzee-derived replication-defective adenovirus (ChAd) vaccine also rapidly induced uniform protection against acute lethal EBOV challenge in macaques. Because protection waned over several months, we boosted ChAd3 With modified vaccinia Ankara (MVA) and generated, for the first time, durable protection against lethal EBOV Challenge.