Passive transfer of antibodies protects immunocompetent and immunodeficient mice against lethal Ebola virus infection without complete inhibition of viral replication

Passive transfer of antibodies protects immunocompetent and immunodeficient mice against lethal Ebola virus infection without complete inhibition of viral replication
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DOI:
10.1128/jvi.75.10.4649-4654.2001
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发表时间:
2001-05-01
影响因子:
5.4
通讯作者:
Rollin, PE
Rollin, PE
中科院分区:
医学2区
文献类型:
--
作者:
Gupta, M;Mahanty, S;Rollin, PE

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埃博拉出血热是一种严重的、通常致命的疾病,由丝状病毒家族成员埃博拉病毒引起。在动物研究中使用非同源免疫血清以及在人类埃博拉出血热的两份轶事报告中使用幸存者血液​​已显示出希望,但这些治疗的功效尚未得到明确证明。我们评估了多克隆免疫血清在埃博拉病毒感染小鼠模型中的保护功效。我们的结果表明,皮下感染活埃博拉病毒的小鼠能够存活并产生高水平的抗埃博拉病毒免疫球蛋白 G (IgG)。在攻击前从这些小鼠中被动转移免疫血清可以保护高达 100% 的幼鼠免受致命的埃博拉病毒感染。保护作用与抗埃博拉病毒 IgG 滴度水平相关,而高滴度抗血清的被动治疗与病毒复制高峰期的延迟相关。将免疫血清转移到 SCID 小鼠体内,在受到埃博拉病毒致死攻击后,小鼠的存活率为 100%,这表明仅抗体就可以预防致命疾病。因此,抗体抑制或延迟病毒生长,提供针对致命埃博拉病毒感染的保护,并且可能不需要其他免疫成分的参与来提供保护。
Ebola hemorrhagic fever is a severe, usually fatal illness caused by Ebola virus, a member of the filovirus family. The use of nonhomologous immune serum in animal studies and blood from survivors in two anecdotal reports of Ebola hemorrhagic fever in humans has shown promise, but the efficacy of these treatments has not been demonstrated definitively. We have evaluated the protective efficacy of polyclonal immune serum in a mouse model of Ebola virus infection. Our results demonstrate that mice infected subcutaneously with live Ebola virus survive infection and generate high levels of anti-Ebola virus immunoglobulin G (IgG). Passive transfer of immune serum from these mice before challenge protected upto 100% of naive mice against lethal Ebola virus infection. Protection correlated with the level of anti-Ebola virus IgG titers, and passive treatment with high-titer antiserum was associated with a delay in the peak of viral replication. Transfer of immune serum to SCID mice resulted in 100% survival after lethal challenge with Ebola virus, indicating that antibodies alone can protect from lethal disease. Thus antibodies suppress or delay viral growth, provide protection against lethal Ebola virus infection, and may not require participation of other immune components for protection.