Neutralizing antibody fails to impact the course of Ebola virus infection in monkeys.
Neutralizing antibody fails to impact the course of Ebola virus infection in monkeys.
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DOI：
10.1371/journal.ppat.0030009
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发表时间：
2007-01
期刊：
影响因子：
6.7
通讯作者：
Burton, Dennis R
中科院分区：
文献类型：
--
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
使用高剂量的中和抗体进行预防，通常可以防止病毒产生急性感染。在这项研究中，我们研究了中和性人源单克隆抗体KZ52在恒河猴体内抵抗埃博拉病毒的能力。这种抗体以前被证明可以完全保护豚鼠免受感染。4只恒河猴在用1000个血小板形成单位的埃博拉病毒攻毒前1天静脉注射50 mg/kg的中和性人单克隆抗体KZ52，然后在攻毒后4天注射第二剂50 mg/kg的抗体。对照动物在没有抗体治疗的情况下暴露于病毒。中和性人单克隆抗体的被动转移不仅不能保护猕猴免受埃博拉病毒的攻击，而且对感染后病毒的爆炸性复制的影响也很小。我们表明，抗体无法影响感染不是由于中和逃逸。埃博拉病毒似乎具有一种在猕猴体内的感染传播机制，即使对高浓度的中和抗体也不敏感。埃博拉病毒是最令人恐惧的人类病原体之一，其死亡率可接近90%，病程极快，可在感染后几天内导致死亡。在培养物中能够抑制病毒感染的抗体，中和抗体，通常可以在感染前存在足够浓度的情况下预防动物和人类的病毒感染。这种中和抗体可以通过被动给药或通过接种疫苗诱导获得。我们之前已经证明，人类中和抗体可以保护豚鼠免受埃博拉病毒的侵害。然而，我们在这里表明，这种抗体并不能保护猴子免受埃博拉病毒的侵害，令人惊讶的是，尽管这种抗体在猴子的血液中含量很高，但它对快速感染过程的影响似乎很小。我们的结论是，在接触埃博拉病毒之前或之后立即使用抗体，例如在研究环境中的事故或生物恐怖袭击之后，不太可能有效预防疾病。最近通过疫苗接种保护猴子免受埃博拉病毒侵害的成功可能不依赖于抗体，或者更有可能严重依赖于抗体和细胞免疫的合作。
Prophylaxis with high doses of neutralizing antibody typically offers protection against challenge with viruses producing acute infections. In this study, we have investigated the ability of the neutralizing human monoclonal antibody, KZ52, to protect against Ebola virus in rhesus macaques. This antibody was previously shown to fully protect guinea pigs from infection. Four rhesus macaques were given 50 mg/kg of neutralizing human monoclonal antibody KZ52 intravenously 1 d before challenge with 1,000 plaque-forming units of Ebola virus, followed by a second dose of 50 mg/kg antibody 4 d after challenge. A control animal was exposed to virus in the absence of antibody treatment. Passive transfer of the neutralizing human monoclonal antibody not only failed to protect macaques against challenge with Ebola virus but also had a minimal effect on the explosive viral replication following infection. We show that the inability of antibody to impact infection was not due to neutralization escape. It appears that Ebola virus has a mechanism of infection propagation in vivo in macaques that is uniquely insensitive even to high concentrations of neutralizing antibody. Ebola virus is one of the most feared of human pathogens with a mortality that can approach 90% and an extremely rapid disease course that can lead to death within days of infection. Antibodies able to inhibit viral infection in culture, neutralizing antibodies, can typically prevent viral infection in animals and humans when present prior to infection, at sufficient concentration. Such neutralizing antibodies may be provided through passive administration or induced by vaccination. We have previously shown that a human neutralizing antibody can protect guinea pigs against Ebola virus. However, here we show that this antibody does not protect monkeys against Ebola virus and surprisingly appears to have very little impact upon the rapid course of infection, despite being present at very high levels in the blood of the monkeys. We conclude that administering antibody prior to or immediately following exposure to Ebola virus, for example, after an accident in a research setting or a bioterrorist attack, is unlikely to be effective in preventing disease. Recent successes in protecting monkeys against Ebola virus through vaccination may be independent of antibody, or, more likely, critically dependent on the cooperation of antibody and cellular immunity.