2011年12月1日是“世界艾滋病日”,，英國《自然》雜志網(wǎng)站11月30日刊登了來自美國加州理工學(xué)院等機構(gòu)研究人員的最新研究成果"Antibody-based protection against HIV infection by vectored immunoprophylaxis”,，他們探索出的一種艾滋病基因療法在動物實驗中取得成效。實驗證明感染大劑量艾滋病病毒的實驗鼠也可受到保護,。
美國加州理工學(xué)院等機構(gòu)的研究人員報告說，通過使用一種經(jīng)過改造的腺病毒，可以在實驗鼠肌肉細胞的基因序列中加入一段代碼,，使得肌肉細胞能夠生成和分泌一些抗體,。這些抗體具有幫助機體抑制艾滋病病毒的作用,，最初是在一些對艾滋病有抵抗力的患者體內(nèi)分離得到的,。
研究人員用這種基因療法測試了5種不同抗體的效果，結(jié)果發(fā)現(xiàn),，兩種代號為B12和VRC01的抗體效果尤其良好,。即使對實驗鼠施加比天然感染艾滋病所需病毒量高出100倍的病毒劑量,，這兩種抗體也能起到完全且持續(xù)的保護效果,，實驗鼠在接受治療一年后仍能避免發(fā)病,。這是因為實驗鼠的肌肉細胞在基因序列被改變后,，會持續(xù)生成相關(guān)抗體并釋放到血液中。
參與研究的戴維·巴爾的摩說，動物實驗的成功為接下來開展人類臨床試驗鋪平了道路,。雖然通常只用基因療法治療遺傳病,，但目前在與艾滋病的斗爭中還沒找到完全有效的療法,，因此基因治療艾滋病值得一試,。
據(jù)介紹,，這種療法可能導(dǎo)致相關(guān)細胞的基因序列永久性改變,，或許會帶來副作用。研究人員希望能在臨床試驗中確定該基因療法是否有副作用并找到規(guī)避方法,。(生物谷Bioon.com)
doi:10.1038/nature10660
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Antibody-based protection against HIV infection by vectored immunoprophylaxis
Alejandro B. Balazs,Joyce Chen,Christin M. Hong,Dinesh S. Rao,Lili Yang& David Baltimore
Despite tremendous efforts, development of an effective vaccine against human immunodeficiency virus (HIV) has proved an elusive goal. Recently, however, numerous antibodies have been identified that are capable of neutralizing most circulating HIV strains. These antibodies all exhibit an unusually high level of somatic mutation, presumably owing to extensive affinity maturation over the course of continuous exposure to an evolving antigen. Although substantial effort has focused on the design of immunogens capable of eliciting antibodies that would target similar epitopes, it remains uncertain whether a conventional vaccine will be able to elicit analogues of the existing broadly neutralizing antibodies. As an alternative to immunization, vector-mediated gene transfer could be used to engineer secretion of the existing broadly neutralizing antibodies into the circulation. Here we describe a practical implementation of this approach, which we call vectored immunoprophylaxis (VIP), which in mice induces lifelong expression of these monoclonal antibodies at high concentrations from a single intramuscular injection. This is achieved using a specialized adeno-associated virus vector optimized for the production of full-length antibody from muscle tissue. We show that humanized mice receiving VIP appear to be fully protected from HIV infection, even when challenged intravenously with very high doses of replication-competent virus. Our results suggest that successful translation of this approach to humans may produce effective prophylaxis against HIV.
