A multifunctional human monoclonal neutralizing antibody that targets a unique conserved epitope on influenza HA.
A multifunctional human monoclonal neutralizing antibody that targets a unique conserved epitope on influenza HA.
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DOI：
10.1038/s41467-018-04704-9
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发表时间：
2018-07-10
影响因子：
16.6
通讯作者：
Crowe JE Jr
中科院分区：
文献类型：
--
作者：
Bangaru S;Zhang H;Gilchuk IM;Voss TG;Irving RP;Gilchuk P;Matta P;Zhu X;Lang S;Nieusma T;Richt JA;Albrecht RA;Vanderven HA;Bombardi R;Kent SJ;Ward AB;Wilson IA;Crowe JE Jr
季节性流感病毒抗原漂移率高，需要经常更换疫苗成分。最近的季节性H3疫苗不能预防最近引起严重人类感染的猪源H3 N2变异株（H3 N2 v）。在这里，我们报告了一种人VH 1 -69基因编码的单克隆抗体（mAb）命名为H3 v-47，表现出强大的交叉反应中和活性，对人类和猪H3 N2病毒，自1989年以来，循环。用H3 N2 v血凝素（HA）对H3 v-47 Fab的晶体结构和电子显微镜重建鉴定了跨越残留酯酶和受体结合亚结构域的独特表位，其不同于任何已知的甲型流感H3病毒中和抗体的表位。MAb H3 v-47主要通过阻断病毒从受感染细胞中流出发挥作用。有趣的是，H3 v-47还与Fcγ受体结合并介导抗体依赖性细胞毒性（ADCC）。这一新发现的保守表位可用于设计新的免疫原，以开发具有广泛保护性的H3疫苗。广泛中和抗体是潜在的治疗剂，可以帮助合理的疫苗开发。在这里，作者表明，人类单克隆抗体H3 v-47识别H3 N2病毒HA中的高度保守表位，通过阻断出口和其他机制抑制病毒复制，并保护小鼠免受疾病的侵害。
The high rate of antigenic drift in seasonal influenza viruses necessitates frequent changes in vaccine composition. Recent seasonal H3 vaccines do not protect against swine-origin H3N2 variant (H3N2v) strains that recently have caused severe human infections. Here, we report a human VH1-69 gene-encoded monoclonal antibody (mAb) designated H3v-47 that exhibits potent cross-reactive neutralization activity against human and swine H3N2 viruses that circulated since 1989. The crystal structure and electron microscopy reconstruction of H3v-47 Fab with the H3N2v hemagglutinin (HA) identify a unique epitope spanning the vestigial esterase and receptor-binding subdomains that is distinct from that of any known neutralizing antibody for influenza A H3 viruses. MAb H3v-47 functions largely by blocking viral egress from infected cells. Interestingly, H3v-47 also engages Fcγ receptor and mediates antibody dependent cellular cytotoxicity (ADCC). This newly identified conserved epitope can be used in design of novel immunogens for development of broadly protective H3 vaccines. Broadly neutralizing antibodies are potential therapeutics and can aid rational vaccine development. Here, the authors show that the human monoclonal antibody H3v-47 recognizes a highly conserved epitope in HA of H3N2 viruses, inhibits virus replication by blocking egress and other mechanisms, and protects mice from disease.
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影响因子：
6.1
作者：
CONNOLLY, ML
通讯作者：
CONNOLLY, ML
DOI：
10.1073/pnas.1609316113
发表时间：
2016-10-18
影响因子：
11.1
作者：
He, Wenqian;Tan, Gene S.;Miller, Matthew S.
通讯作者：
Miller, Matthew S.
DOI：
10.1073/pnas.1319058110
发表时间：
2014-01-07
影响因子：
11.1
作者：
Friesen, Robert H. E.;Lee, Peter S.;Wilson, Ian A.
通讯作者：
Wilson, Ian A.
影响因子：
33.9
作者：
Blanton, Lenee;Kniss, Krista;Brammer, Lynnette
通讯作者：
Brammer, Lynnette
DOI：
10.1107/s0907444909052925
发表时间：
2010-02
期刊：
Acta crystallographica. Section D, Biological crystallography
影响因子：
--
作者：
Adams PD;Afonine PV;Bunkóczi G;Chen VB;Davis IW;Echols N;Headd JJ;Hung LW;Kapral GJ;Grosse-Kunstleve RW;McCoy AJ;Moriarty NW;Oeffner R;Read RJ;Richardson DC;Richardson JS;Terwilliger TC;Zwart PH
通讯作者：
Zwart PH