Sustained protection against Ebola virus infection following treatment of infected nonhuman primates with ZMAb

Sustained protection against Ebola virus infection following treatment of infected nonhuman primates with ZMAb
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DOI:
10.1038/srep03365
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发表时间:
2013-11-28
期刊:
影响因子:
4.6
通讯作者:
Kobinger, Gary P.
Kobinger, Gary P.
中科院分区:
综合性期刊3区
文献类型:
--
作者:
Qiu, Xiangguo;Audet, Jonathan;Kobinger, Gary P.

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埃博拉病毒(EBOV)是最致命的丝状病毒之一,人类死亡率高达90%。此前,我们证明了在暴露后24小时或48小时分别给予3种EBOV-GP特异性单克隆抗体(ZMAb)的组合,感染EBOV的食蟹猴的存活率分别为100%和50%。存活者表现出EBOV-GP特异性体液和细胞介导的免疫应答。为了评价在ZMAb处理和EBOV攻击期间在NHP中诱导的免疫应答是否足以保护存活者免受随后的暴露,在初始攻击后10或13周对在初始攻击中存活的动物进行再攻击。在10周时再激发的动物全部存活,而在13周时再激发的6只动物中有4只存活。数据表明,在用EBOV成功治疗EBOV感染的NHP期间产生了强有力的免疫应答,这导致针对第二次致死暴露的持续保护。
Ebola virus (EBOV) is one of the most lethal filoviruses, with mortality rates of up to 90% in humans. Previously, we demonstrated 100% and 50% survival of EBOV-infected cynomologus macaques with a combination of 3 EBOV-GP-specific monoclonal antibodies (ZMAb) administered at 24 or 48 hours post-exposure, respectively. The survivors demonstrated EBOV-GP-specific humoral and cell-mediated immune responses. In order to evaluate whether the immune response induced in NHPs during the ZMAb treatment and EBOV challenge is sufficient to protect survivors against a subsequent exposure, animals that survived the initial challenge were rechallenged at 10 or 13 weeks after the initial challenge. The animals rechallenged at 10 weeks all survived whereas 4 of 6 animals survived a rechallenge at 13 weeks. The data indicate that a robust immune response was generated during the successful treatment of EBOV-infected NHPs with EBOV, which resulted in sustained protection against a second lethal exposure.