The human immune response to Dengue virus is dominated by highly cross-reactive antibodies endowed with neutralizing and enhancing activity.
The human immune response to Dengue virus is dominated by highly cross-reactive antibodies endowed with neutralizing and enhancing activity.
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DOI：
10.1016/j.chom.2010.08.007
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发表时间：
2010-09-16
影响因子：
30.3
通讯作者：
Sallusto F
中科院分区：
文献类型：
--
作者：
Beltramello M;Williams KL;Simmons CP;Macagno A;Simonelli L;Quyen NT;Sukupolvi-Petty S;Navarro-Sanchez E;Young PR;de Silva AM;Rey FA;Varani L;Whitehead SS;Diamond MS;Harris E;Lanzavecchia A;Sallusto F
抗体可预防同源登革热病毒（DENV）感染，但也可通过Fcγ受体（FcγR）促进异型病毒进入，从而引发重症登革热。我们使初次或二次感染后的个体的记忆B细胞永生化，并分析了由此产生的抗登革热单克隆抗体（mAbs）。针对包膜（E）蛋白结构域III（DIII）的单克隆抗体具有血清型特异性或交叉反应性，且能有效中和登革热病毒感染。针对DI/DII或病毒膜蛋白prM的单克隆抗体中和能力较弱，并与四种登革热病毒血清型表现出广泛的交叉反应性。所有单克隆抗体在亚中和浓度下都会增强感染。三种针对四种登革热病毒血清型上不同表位且经改造以防止FcγR结合的单克隆抗体不会增强感染，并在体外和体内（在致死性登革热病毒感染的小鼠模型中作为暴露后治疗）中和登革热病毒。我们的研究结果揭示了人类抗登革热抗体中出乎意料的交叉反应程度，并阐明了基于抗体的疗法用于控制重症登革热的潜力。
Antibodies protect against homologous Dengue virus (DENV) infection but can precipitate severe dengue by promoting heterotypic virus entry via Fcγ receptors (FcγR). We immortalized memory B cells from individuals after primary or secondary infection and analyzed anti-DENV monoclonal antibodies (mAbs) thus generated. MAbs to envelope (E) protein domain III (DIII) were either serotype specific or cross-reactive and potently neutralized DENV infection. DI/DII- or viral membrane protein prM-reactive mAbs neutralized poorly and showed broad cross-reactivity with the four DENV serotypes. All mAbs enhanced infection at subneutralizing concentrations. Three mAbs targeting distinct epitopes on the four DENV serotypes and engineered to prevent FcγR binding did not enhance infection and neutralized DENV in vitro and in vivo as postexposure therapy in a mouse model of lethal DENV infection. Our findings reveal an unexpected degree of cross-reactivity in human antibodies against DENV and illustrate the potential for an antibody-based therapy to control severe dengue.
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影响因子：
6.7
作者：
Balsitis SJ;Williams KL;Lachica R;Flores D;Kyle JL;Mehlhop E;Johnson S;Diamond MS;Beatty PR;Harris E
通讯作者：
Harris E
DOI：
10.1073/pnas.0703498104
发表时间：
2007-05-29
影响因子：
11.1
作者：
Goncalvez, Ana P.;Engle, Ronald E.;Lai, Ching-Juh
通讯作者：
Lai, Ching-Juh
影响因子：
3.8
作者：
GOULD, EA;BUCKLEY, A;VARMA, MGR
通讯作者：
VARMA, MGR
影响因子：
5.4
作者：
Goncalvez, AP;Men, R;Lai, CJ
通讯作者：
Lai, CJ
影响因子：
5.4
作者：
Bhardwaj, S;Holbrook, M;Watowich, SJ
通讯作者：
Watowich, SJ