[转移贴]1918流感幸存者令抗体复兴

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原贴由论坛会员Rojjer发表于 2008-8-19 11:08：

美国的研究指出，死亡惨重的1918年流感大爆发的幸存者仍然享有对该病毒的免疫能力。据英国广播公司报道，美国科学家们发现，从大爆发当中活了过来的人们仍然可以制造杀死H1N1流感的抗体。

这项8月17日在线发表于《自然》（Nature）杂志的研究成果或可帮助开发用于未来大爆发时的紧急治疗药物。

1918年的西班牙流感疫情估计造成了5000万人死亡。一些专家说那是历史上破坏最严重的流行病疫情，连健康的成年人也受到波及。科学家还没有完全明白为什么杀伤力会这么大，但是他们担忧禽流感会带来新的爆发，而且会是同样的具杀伤力。不过，科学家们现在找到了应对这种爆发的新途径。

他们对32名在1918年流感中活了过来的人，发现全部人的血液里面仍有破坏病毒的抗体。 部分自愿者——年龄介乎91到101岁——甚至有着制造这些抗体的细胞。 研究人员们利用这些抗体来治疗受到感染的白老鼠，据他们说，结果显示90年后的今天，这些流感幸存者仍然受到保护。 这些抗体的效力还十分强劲，只需要很少的剂量就足以杀死病毒。

范德堡大学的克罗博士参与了研究的领导工作。他说可以开发类似的抗体，用以破坏新品种的禽流感病毒.


cite from:http://www.sciencenet.cn/htmlpaper/2008819958348713164.html

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Nature advance online publication 17 August 2008 | doi:10.1038/nature07231; Received 7 April 2008; Accepted 3 July 2008; Published online 17 August 2008

Neutralizing antibodies derived from the B cells of 1918 influenza pandemic survivors

Xiaocong Yu1,6, Tshidi Tsibane2,6, Patricia A. McGraw1, Frances S. House1, Christopher J. Keefer1, Mark D. Hicar1, Terrence M. Tumpey3, Claudia Pappas2,3, Lucy A. Perrone3, Osvaldo Martinez2, James Stevens3,4, Ian A. Wilson4, Patricia V. Aguilar2, Eric L. Altschuler5, Christopher F. Basler2 & James E. Crowe Jr1

Departments of Pediatrics and of Microbiology and Immunology, Vanderbilt University Medical Center, Nashville, Tennessee 37232, USA
Department of Microbiology, Mount Sinai School of Medicine, New York 10029, USA
Influenza Division, Centers for Disease Control and Prevention, Atlanta, Georgia 30333, USA
Department of Molecular Biology and Skaggs Institute for Chemical Biology, The Scripps Research Institute, La Jolla, California 92037, USA
Department of Physical Medicine and Rehabilitation, University of Medicine & Dentistry of New Jersey, Newark, New Jersey 07103, USA
These authors contributed equally to this work.
Correspondence to: Eric L. Altschuler5Christopher F. Basler2James E. Crowe Jr1 Correspondence and requests for materials should be addressed to J.E.C. (Email: James.Crowe@vanderbilt.edu), C.F.B. (Email: Chris.Basler@mssm.edu), or E.L.A. (Email: altschel@umdnj.edu).


Top of pageInvestigation of the human antibody response to influenza virus infection has been largely limited to serology, with relatively little analysis at the molecular level. The 1918 H1N1 influenza virus pandemic was the most severe of the modern era1. Recent work has recovered the gene sequences of this unusual strain2, so that the 1918 pandemic virus could be reconstituted to display its unique virulence phenotypes3, 4. However, little is known about adaptive immunity to this virus. We took advantage of the 1918 virus sequencing and the resultant production of recombinant 1918 haemagglutinin (HA) protein antigen to characterize at the clonal level neutralizing antibodies induced by natural exposure of survivors to the 1918 pandemic virus. Here we show that of the 32 individuals tested that were born in or before 1915, each showed seroreactivity with the 1918 virus, nearly 90 years after the pandemic. Seven of the eight donor samples tested had circulating B cells that secreted antibodies that bound the 1918 HA. We isolated B cells from subjects and generated five monoclonal antibodies that showed potent neutralizing activity against 1918 virus from three separate donors. These antibodies also cross-reacted with the genetically similar HA of a 1930 swine H1N1 influenza strain, but did not cross-react with HAs of more contemporary human influenza viruses. The antibody genes had an unusually high degree of somatic mutation. The antibodies bound to the 1918 HA protein with high affinity, had exceptional virus-neutralizing potency and protected mice from lethal infection. Isolation of viruses that escaped inhibition suggested that the antibodies recognize classical antigenic sites on the HA surface. Thus, these studies demonstrate that survivors of the 1918 influenza pandemic possess highly functional, virus-neutralizing antibodies to this uniquely virulent virus, and that humans can sustain circulating B memory cells to viruses for many decades after exposure—well into the tenth decade of life

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简单看了看原文,这篇文章能发在Nature之上毕竟有其独到之处.
没有复杂的实验技术和操作步骤.文章讨论部分个人觉的很是精彩 ,从一个简单的现象推引出一系列关于流感病毒免疫的观点,非抗原依赖的记忆B细胞的维持,体细胞高频突变与抗体效能.记忆B细胞的持续激活的特殊机制等等.最终也提出了其潜在的应用价值.
感兴趣的朋友,详细阅读后谈谈想法哦!