埃博拉病毒颗粒电子显微图片,图片来自维基共享资源。
来自美国陆军传染病医学研究所的军事科学家们首次证实基于抗体的疗法能够成功地保护猴子免受致命性埃博拉病毒和马尔堡病毒感染。此外,甚至是感染后两天进行抗体治疗,这些猴子也得到全面的保护。迄今为止,这一成就不是任何抵抗这些病毒的实验性治疗方法所能比拟的。相关研究结果于2012年3月12日发表在PNAS期刊上。
属于线状病毒的埃博拉病毒和马尔堡病毒导致人患上出血热(hemorrhagic fever),病死率高达90%。它们是一种全球性健康问题,且被认为是潜在性的生物威胁因子。当前,还没有获得批准上市进行销售的疫苗或疗法用于人类治疗,这就使得开发这些产品成为当务之急。
在这篇论文中,来自美国陆军传染病医学研究所的John M. Dye、Andrew S. Herbert、William D. Pratt和同事们在受控实验室条件下,让一些猴子接触致死剂量的丝状病毒,然后从存活下来的猴子体内提取抗体。这些存活下来的猴子产生高水平的抗体来抵抗这些传染病。研究人员从它们身上收集血清,进行抗体纯化,并对纯化的抗体进行病毒中和活性测试,然后开展进一步实验。
在第一项研究中,感染马尔堡病毒的猴子在感染15到30分钟后用抗体进行治疗,然后在感染后第4天和第8天再进行治疗。这些猴子完全得到保护,没有表现出任何疾病症状,而且在它们的血液里也不存在可检测到的病毒水平。再者,所有猴子对马尔堡病毒产生免疫应答,而且当这种病毒再次侵袭时都能够存活下来。
在接下来一系列实验中,猴子感染上埃博拉病毒或者马尔堡病毒,在感染2天后对它们进行抗体治疗,然后在感染后第4天和第8天再进行治疗。抗体延迟治疗同样保护这两组猴子(一组感染埃博拉病毒,一组感染马尔堡病毒)免受侵袭。在每组中,三只猴子中有两只在治疗后没有表现出临床疾病症状,而第三只猴子在完全康复后产生轻微的症状。
在过去将近十年里,丝状病毒研究科学界因为大量尝试利用抗体保护猴子免受丝状病毒侵袭的实验都遭遇失败,因而不重视基于抗体的疗法。
Dye说,“利用抗体来治疗传染病是一种相当娴熟的技术,而且美国食品药品监督局也已批准多种基于抗体开发出来的产品。根据这些发现,我们证实基于抗体的疗法确实能够用来有效地治疗丝状病毒感染。”
Dye说,他们希望这项研究能够为人们开发出用于人类的抗丝状病毒疗法提供新的方法。(生物谷:towersimper编译)
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doi:10.1073/pnas.1200409109
PMC:
PMID:
Postexposure antibody prophylaxis protects nonhuman primates from filovirus disease
John M. Dye, Andrew S. Herbert, Ana I. Kuehne, James F. Barth, Majidat A. Muhammad, Samantha E. Zak, Ramon A. Ortiz, Laura I. Prugar, and William D. Pratt
Antibody therapies to prevent or limit filovirus infections have received modest interest in recent years, in part because of early negative experimental evidence. We have overcome the limitations of this approach, leveraging the use of antibody from nonhuman primates (NHPs) that survived challenge to filoviruses under controlled conditions. By using concentrated, polyclonal IgG antibody from these survivors, we treated filovirus-infected NHPs with multiple doses administered over the clinical phase of disease. In the first study, Marburg virus (MARV)-infected NHPs were treated 15 to 30 min postexposure with virus-specific IgG, with additional treatments on days 4 and 8 postexposure. The postexposure IgG treatment was completely protective, with no signs of disease or detectable viremia. MARV-specific IgM antibody responses were generated, and all macaques survived rechallenge with MARV, suggesting that they generated an immune response to virus replication. In the next set of studies, NHPs were infected with MARV or Ebola virus (EBOV), and treatments were delayed 48 h, with additional treatments on days 4 and 8 postexposure. The delayed treatments protected both MARV- and EBOV-challenged NHPs. In both studies, two of the three IgG-treated NHPs had no clinical signs of illness, with the third NHP developing mild and delayed signs of disease followed by full recovery. These studies clearly demonstrate that postexposure antibody treatments can protect NHPs and open avenues for filovirus therapies for human use using established Food and Drug Administration-approved polyclonal or monoclonal antibody technologies.