Protective efficacy of neutralizing monoclonal antibodies in a nonhuman primate model of Ebola hemorrhagic fever.
Protective efficacy of neutralizing monoclonal antibodies in a nonhuman primate model of Ebola hemorrhagic fever.
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DOI：
10.1371/journal.pone.0036192
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发表时间：
2012
期刊：
影响因子：
3.7
通讯作者：
Takada A
中科院分区：
文献类型：
--
作者：
Marzi A;Yoshida R;Miyamoto H;Ishijima M;Suzuki Y;Higuchi M;Matsuyama Y;Igarashi M;Nakayama E;Kuroda M;Saijo M;Feldmann F;Brining D;Feldmann H;Takada A
埃博拉病毒（Ebola virus，EBOV）是引起灵长类动物严重出血热的病原体，人类病死率高达90%。今天，既没有获得许可的疫苗，也没有治疗埃博拉出血热（EHF）的方法。扎伊尔埃博拉病毒（ZEBOV）特异性单克隆抗体（MAbs）已成功地用于啮齿动物模型的被动免疫实验，但未能保护非人灵长类动物免受致命疾病。在这项研究中，我们使用了两个克隆的人-鼠嵌合单克隆抗体（ch 133和ch 226），具有很强的中和活性，对ZEBOV和评估其保护潜力的恒河猴模型的EHF。在攻毒前24小时和攻毒后24小时和72小时，在静脉给予MAb ch 133和ch 226联合给药的动物中观察到病毒载量降低和部分保护。MAb在存活动物的血液中循环，直到检测到病毒诱导的IgG应答。相比之下，在死于感染的动物中，血清MAb浓度在疾病的终末期降低至不可检测的水平，表明由于病毒复制，这些抗体大量消耗。因此，血清单克隆抗体的快速下降与非幸存者中病毒血症的增加明显相关。我们的研究结果表明，EBOV中和抗体，特别是与其他治疗策略相结合，可能有利于减少病毒载量和延长EHF期间的疾病进展。
Ebola virus (EBOV) is the causative agent of severe hemorrhagic fever in primates, with human case fatality rates up to 90%. Today, there is neither a licensed vaccine nor a treatment available for Ebola hemorrhagic fever (EHF). Single monoclonal antibodies (MAbs) specific for Zaire ebolavirus (ZEBOV) have been successfully used in passive immunization experiments in rodent models, but have failed to protect nonhuman primates from lethal disease. In this study, we used two clones of human-mouse chimeric MAbs (ch133 and ch226) with strong neutralizing activity against ZEBOV and evaluated their protective potential in a rhesus macaque model of EHF. Reduced viral loads and partial protection were observed in animals given MAbs ch133 and ch226 combined intravenously at 24 hours before and 24 and 72 hours after challenge. MAbs circulated in the blood of a surviving animal until virus-induced IgG responses were detected. In contrast, serum MAb concentrations decreased to undetectable levels at terminal stages of disease in animals that succumbed to infection, indicating substantial consumption of these antibodies due to virus replication. Accordingly, the rapid decrease of serum MAbs was clearly associated with increased viremia in non-survivors. Our results indicate that EBOV neutralizing antibodies, particularly in combination with other therapeutic strategies, might be beneficial in reducing viral loads and prolonging disease progression during EHF.
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影响因子：
6.7
作者：
Oswald, Wendelien B;Geisbert, Thomas W;Davis, Kelly J;Geisbert, Joan B;Sullivan, Nancy J;Jahrling, Peter B;Parren, Paul W H I;Burton, Dennis R
通讯作者：
Burton, Dennis R
影响因子：
3.7
作者：
Shedlock DJ;Bailey MA;Popernack PM;Cunningham JM;Burton DR;Sullivan NJ
通讯作者：
Sullivan NJ
影响因子：
5.4
作者：
Maruyama, T;Rodriguez, LL;Burton, DR
通讯作者：
Burton, DR
DOI：
10.1073/pnas.93.8.3602
发表时间：
1996-04-16
影响因子：
11.1
作者：
Sanchez, A;Trappier, SG;Nichol, ST
通讯作者：
Nichol, ST
影响因子：
9.4
作者：
Saijo, M;Niikura, M;Kurane, I
通讯作者：
Kurane, I