Neutralizing antibodies derived from the B cells of 1918 influenza pandemic survivors.
Neutralizing antibodies derived from the B cells of 1918 influenza pandemic survivors.
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DOI：
10.1038/nature07231
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发表时间：
2008-09-25
期刊：
影响因子：
64.8
通讯作者：
Crowe, James E., Jr.
中科院分区：
文献类型：
--
作者：
Yu, Xiaocong;Tsibane, Tshidi;McGraw, Patricia A.;House, Frances S.;Keefer, Christopher J.;Hicar, Mark D.;Tumpey, Terrence M.;Pappas, Claudia;Perrone, Lucy A.;Martinez, Osvaldo;Stevens, James;Wilson, Ian A.;Aguilar, Patricia V.;Altschuler, Eric L.;Basler, Christopher F.;Crowe, James E., Jr.
对流感病毒感染的人抗体应答的研究主要限于血清学，在分子水平上的分析相对较少。1918年H1N1流感病毒大流行是现代最严重的一次。最近的工作已经恢复了这种不寻常毒株的基因序列，因此1918年大流行病毒可以重组以显示其独特的毒力表型。然而，人们对这种病毒的适应性免疫知之甚少。我们利用1918年病毒测序和重组1918血凝素（HA）蛋白抗原的产生，在克隆水平上表征幸存者自然暴露于1918年大流行病毒诱导的中和抗体。在我们的研究中，32名出生于1915年或之前的受试者中的每一个人都表现出对1918年病毒的血清反应性，距离大流行已经过去了近90年。检测的8份供体样品中有7份具有分泌结合1918 HA的抗体的循环B细胞。我们从受试者中分离出B细胞，并产生了五种单克隆抗体，这些抗体对来自三个不同供体的1918病毒表现出有效的中和活性。这些抗体也与1930年猪H1N1流感病毒株的遗传相似的HA交叉反应，但不与更现代的人类流感病毒的HA交叉反应。抗体基因表现出异常高程度的体细胞突变。抗体以高亲和力结合1918 HA蛋白，表现出优异的病毒中和效力，并保护小鼠免受致死性感染。逃避抑制的病毒的分离表明抗体识别HA表面上的经典抗原位点。因此，这些研究表明，1918年流感大流行的幸存者拥有针对这种独特毒性病毒的高功能病毒中和抗体，并且人类可以在接触病毒后的数十年内维持循环B记忆细胞-直到生命的第十个十年。
Investigation 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 era. Recent work has recovered the gene sequences of this unusual strain, so that the 1918 pandemic virus could be reconstituted to display its unique virulence phenotypes. 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 hemagglutinin (HA) protein antigen to characterize at the clonal level neutralizing antibodies induced by natural exposure of survivors to the 1918 pandemic virus. In our study, each of 32 individuals tested that were born in or before 1915 exhibited seroreactivity with 1918 virus, nearly 90 years after the pandemic. Seven of 8 donor samples tested had circulating B cells that secreted antibodies that bound 1918 HA. We isolated B cells from subjects and generated five monoclonal antibodies that exhibited 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 not with HAs of more contemporary human influenza viruses. The antibody genes exhibited an unusually high degree of somatic mutation. The antibodies bound to the 1918 HA protein with high affinity, exhibited 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 reveal 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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影响因子：
2.2
作者：
Yu, Xiaocong;McGraw, Patricia A.;Crowe, James E., Jr.
通讯作者：
Crowe, James E., Jr.
影响因子：
64.8
作者：
Kash, John C.;Tumpey, Terrence M.;Katze, Michael G.
通讯作者：
Katze, Michael G.
影响因子：
4.4
作者：
Crotty, S;Felgner, P;Ahmed, R
通讯作者：
Ahmed, R
DOI：
10.1073/pnas.212519699
发表时间：
2002-10-15
影响因子：
11.1
作者：
Tumpey, TM;García-Sastre, A;Basler, CF
通讯作者：
Basler, CF
影响因子：
64.8
作者：
Taubenberger, JK;Reid, AH;Fanning, TG
通讯作者：
Fanning, TG