H7n9 influenza virus neutralizing antibodies that possess few somatic mutations | |
Thornburg, Natalie J.1,2; Zhang, Heng3,4,14; Bangaru, Sandhya5,6,7; Sapparapu, Gopal1,2; Kose, Nurgun1; Lampley, Rebecca M.1; Bombardi, Robin G.1; Yu, Yingchun1; Graham, Stephen1; Branchizio, Andre1 | |
刊名 | Journal of clinical investigation |
2016-04-01 | |
卷号 | 126期号:4页码:1482-1494 |
ISSN号 | 0021-9738 |
DOI | 10.1172/jci85317 |
通讯作者 | Crowe, james e., jr.(james.crowe@vanderbilt.edu) |
英文摘要 | Avian h7n9 influenza viruses are group 2 influenza a viruses that have been identified as the etiologic agent for a current major outbreak that began in china in 2013 and may pose a pandemic threat. here, we examined the human h7-reactive antibody response in 75 recipients of a monovalent inactivated a/shanghai/02/2013 h7n9 vaccine. after 2 doses of vaccine, the majority of donors had memory b cells that secreted iggs specific for h7 ha, with dominant responses against single ha subtypes, although frequencies of h7-reactive b cells ranged widely between donors. we isolated 12 naturally occurring mabs with low half-maximal effective concentrations for binding, 5 of which possessed neutralizing and ha-inhibiting activities. the 5 neutralizing mabs exhibited narrow breadth of reactivity with influenza h7 strains. epitope-mapping studies using neutralization escape mutant analysis, deuterium exchange mass spectrometry, and x-ray crystallography revealed that these neutralizing mabs bind near the receptor-binding pocket on ha. all 5 neutralizing mabs possessed low numbers of somatic mutations, suggesting the clones arose from naive b cells. the most potent mab, h7.167, was tested as a prophylactic treatment in a mouse intranasal virus challenge study, and systemic administration of the mab markedly reduced viral lung titers. |
WOS关键词 | EXCHANGE MASS-SPECTROMETRY ; RESPIRATORY DROPLET ; RECEPTOR-BINDING ; AVIAN INFLUENZA ; HIGH-THROUGHPUT ; HUMAN INFECTION ; A VIRUSES ; HEMAGGLUTININ ; ORIGIN ; VACCINE |
WOS研究方向 | Research & Experimental Medicine |
WOS类目 | Medicine, Research & Experimental |
语种 | 英语 |
出版者 | AMER SOC CLINICAL INVESTIGATION INC |
WOS记录号 | WOS:000373522300036 |
内容类型 | 期刊论文 |
URI标识 | http://www.corc.org.cn/handle/1471x/2176519 |
专题 | 高能物理研究所 |
通讯作者 | Crowe, James E., Jr. |
作者单位 | 1.Vanderbilt Univ, Vanderbilt Vaccine Ctr, 221 Kirkland Hall, Nashville, TN 37235 USA 2.Vanderbilt Univ, Dept Pediat, Nashville, TN USA 3.Scripps Res Inst, Dept Integrat Struct & Computat Biol, La Jolla, CA 92037 USA 4.Scripps Res Inst, Skaggs Inst Chem Biol, La Jolla, CA 92037 USA 5.Vanderbilt Univ, Dept Pathol, Nashville, TN USA 6.Vanderbilt Univ, Dept Microbiol, 221 Kirkland Hall, Nashville, TN 37235 USA 7.Vanderbilt Univ, Dept Immunol, 221 Kirkland Hall, Nashville, TN 37235 USA 8.Vanderbilt Univ, Vanderbilt Vaccine Res Program, 221 Kirkland Hall, Nashville, TN 37235 USA 9.Univ Calif San Diego, Sch Med, Dept Med, San Diego, CA USA 10.Univ Calif San Diego, Sch Med, Biomed Sci Grad Program, San Diego, CA USA |
推荐引用方式 GB/T 7714 | Thornburg, Natalie J.,Zhang, Heng,Bangaru, Sandhya,et al. H7n9 influenza virus neutralizing antibodies that possess few somatic mutations[J]. Journal of clinical investigation,2016,126(4):1482-1494. |
APA | Thornburg, Natalie J..,Zhang, Heng.,Bangaru, Sandhya.,Sapparapu, Gopal.,Kose, Nurgun.,...&Crowe, James E., Jr..(2016).H7n9 influenza virus neutralizing antibodies that possess few somatic mutations.Journal of clinical investigation,126(4),1482-1494. |
MLA | Thornburg, Natalie J.,et al."H7n9 influenza virus neutralizing antibodies that possess few somatic mutations".Journal of clinical investigation 126.4(2016):1482-1494. |
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