期刊
CELL
卷 177, 期 5, 页码 1136-+出版社
CELL PRESS
DOI: 10.1016/j.cell.2019.04.011
关键词
-
资金
- NIH [U19 AI117905, R56 AI127371, P01 AI097092, HHSN272201400024C, HHSN272201400008C]
- CTSA award from NCATS [UL1 TR002243]
- NIAID [HHSN27220170041I]
- NCI [ACB-12002]
- NIGMS [AGM-12006]
- DOE Office of Science [DE-AC02-06CH11357]
- U.S. DOE, Office of Science, Office of Basic Energy Sciences [DE-AC02-76SF00515]
- DOE Office of Biological and Environmental Research
- NIH, NIGMS [P41GM103393]
Here, we describe the discovery of a naturally occurring human antibody (Ab), FluA-20, that recognizes a new site of vulnerability on the hemagglutinin (HA) head domain and reacts with most influenza A viruses. Structural characterization of FluA-20 with H1 and H3 head domains revealed a novel epitope in the HA trimer interface, suggesting previously unrecognized dynamic features of the trimeric HA protein. The critical HA residues recognized by FluA-20 remain conserved across most subtypes of influenza A viruses, which explains the Ab's extraordinary breadth. The Ab rapidly disrupted the integrity of HA protein trimers, inhibited cell-to-cell spread of virus in culture, and protected mice against challenge with viruses of H1N1, H3N2, H5N1, or H7N9 subtypes when used as prophylaxis or therapy. The FluA-20 Ab has uncovered an exceedingly conserved protective determinant in the influenza HA head domain trimer interface that is an unexpected new target for anti-influenza therapeutics and vaccines.
作者
我是这篇论文的作者
点击您的名字以认领此论文并将其添加到您的个人资料中。
推荐
暂无数据