埃博拉病毒顆粒電子顯微圖片，圖片來自維基共享資源,。
來自美國陸軍傳染病醫(yī)學(xué)研究所的軍事科學(xué)家們首次證實(shí)基于抗體的療法能夠成功地保護(hù)猴子免受致命性埃博拉病毒和馬爾堡病毒感染。此外,，甚至是感染后兩天進(jìn)行抗體治療,，這些猴子也得到全面的保護(hù)。迄今為止,，這一成就不是任何抵抗這些病毒的實(shí)驗(yàn)性治療方法所能比擬的,。相關(guān)研究結(jié)果于2012年3月12日發(fā)表在PNAS期刊上。
屬于線狀病毒的埃博拉病毒和馬爾堡病毒導(dǎo)致人患上出血熱(hemorrhagic fever),，病死率高達(dá)90%,。它們是一種全球性健康問題，且被認(rèn)為是潛在性的生物威脅因子,。當(dāng)前，還沒有獲得批準(zhǔn)上市進(jìn)行銷售的疫苗或療法用于人類治療,，這就使得開發(fā)這些產(chǎn)品成為當(dāng)務(wù)之急。
在這篇論文中,，來自美國陸軍傳染病醫(yī)學(xué)研究所的John M. Dye,、Andrew S. Herbert,、William D. Pratt和同事們在受控實(shí)驗(yàn)室條件下,，讓一些猴子接觸致死劑量的絲狀病毒,，然后從存活下來的猴子體內(nèi)提取抗體,。這些存活下來的猴子產(chǎn)生高水平的抗體來抵抗這些傳染病,。研究人員從它們身上收集血清,，進(jìn)行抗體純化,，并對純化的抗體進(jìn)行病毒中和活性測試,，然后開展進(jìn)一步實(shí)驗(yàn),。
在第一項(xiàng)研究中,，感染馬爾堡病毒的猴子在感染15到30分鐘后用抗體進(jìn)行治療,，然后在感染后第4天和第8天再進(jìn)行治療,。這些猴子完全得到保護(hù),，沒有表現(xiàn)出任何疾病癥狀，而且在它們的血液里也不存在可檢測到的病毒水平,。再者,，所有猴子對馬爾堡病毒產(chǎn)生免疫應(yīng)答,，而且當(dāng)這種病毒再次侵襲時(shí)都能夠存活下來,。
在接下來一系列實(shí)驗(yàn)中,，猴子感染上埃博拉病毒或者馬爾堡病毒，在感染2天后對它們進(jìn)行抗體治療,，然后在感染后第4天和第8天再進(jìn)行治療?？贵w延遲治療同樣保護(hù)這兩組猴子(一組感染埃博拉病毒，一組感染馬爾堡病毒)免受侵襲,。在每組中,，三只猴子中有兩只在治療后沒有表現(xiàn)出臨床疾病癥狀,，而第三只猴子在完全康復(fù)后產(chǎn)生輕微的癥狀,。
在過去將近十年里,，絲狀病毒研究科學(xué)界因?yàn)榇罅繃L試?yán)每贵w保護(hù)猴子免受絲狀病毒侵襲的實(shí)驗(yàn)都遭遇失敗,，因而不重視基于抗體的療法。
Dye說,，“利用抗體來治療傳染病是一種相當(dāng)嫻熟的技術(shù),，而且美國食品藥品監(jiān)督局也已批準(zhǔn)多種基于抗體開發(fā)出來的產(chǎn)品,。根據(jù)這些發(fā)現(xiàn),，我們證實(shí)基于抗體的療法確實(shí)能夠用來有效地治療絲狀病毒感染,。”
Dye說,，他們希望這項(xiàng)研究能夠?yàn)槿藗冮_發(fā)出用于人類的抗絲狀病毒療法提供新的方法,。(生物谷：towersimper編譯)
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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.
