The Human Immune Response to Dengue Virus Is Dominated by Highly Cross-Reactive Antibodies Endowed with Neutralizing and Enhancing Activity

被引：470

作者：

Beltramello, Martina ^{[1
]}

Williams, Katherine L. ^{[2
]}

Simmons, Cameron P. ^{[3
]}

Macagno, Annalisa ^{[1
]}

Simonelli, Luca ^{[1
]}

Quyen, Nguyen Than Ha ^{[3
]}

Sukupolvi-Petty, Soila ^{[4
,5
,6
]}

Navarro-Sanchez, Erika ^{[7
]}

Young, Paul R. ^{[8
]}

de Silva, Aravinda M. ^{[9
]}

Rey, Felix A. ^{[7
]}

Varani, Luca ^{[1
]}

Whitehead, Stephen S. ^{[10
]}

Diamond, Michael S. ^{[4
,5
,6
]}

Harris, Eva ^{[2
]}

Lanzavecchia, Antonio ^{[1
]}

Sallusto, Federica ^{[1
]}

机构：

[1] Inst Res Biomed, CH-6500 Bellinzona, Switzerland

[2] Univ Calif Berkeley, Div Infect Dis, Berkeley, CA 94720 USA

[3] Univ Oxford, Clin Res Unit, Hosp Trop Dis, Ho Chi Minh City, Vietnam

[4] Washington Univ, Dept Med, Sch Med, St Louis, MO 63110 USA

[5] Washington Univ, Dept Mol Microbiol, Sch Med, St Louis, MO 63110 USA

[6] Washington Univ, Dept Pathol & Immunol, Sch Med, St Louis, MO 63110 USA

[7] Inst Pasteur, Dept Virol, F-75724 Paris, France

[8] Univ Queensland, Sch Chem & Mol Biosci, Ctr Infect Dis Res, Brisbane, Qld 4072, Australia

[9] Univ N Carolina, Dept Microbiol & Immunol, Sch Med, Chapel Hill, NC 27599 USA

[10] NIAID, Infect Dis Lab, NIH, Bethesda, MD 20892 USA

来源：

CELL HOST & MICROBE | 2010年 / 8卷 / 03期

基金：

英国惠康基金; 瑞士国家科学基金会;

关键词：

WEST-NILE-VIRUS; HUMAN MONOCLONAL-ANTIBODIES; IMMUNOGLOBULIN G1 ANTIBODY; CHIMPANZEE FAB FRAGMENTS; BORNE ENCEPHALITIS-VIRUS; PROTEIN DOMAIN-III; ENVELOPE GLYCOPROTEIN; DEPENDENT ENHANCEMENT; HEMORRHAGIC-FEVER; MEDIATED NEUTRALIZATION;

D O I：

10.1016/j.chom.2010.08.007

中图分类号：

Q93 [微生物学];

学科分类号：

071005 ; 100705 ;

摘要：

Antibodies protect against homologous Dengue virus (DENV) infection but can precipitate severe dengue by promoting heterotypic virus entry via Fc gamma receptors (Fc gamma R). 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 Fc gamma R 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.

引用

页码：271 / 283

页数：13

共 64 条

[41] Novel anti-dengue monoclonal antibody recognizing conformational structure of the prM-E heterodimeric complex of dengue virus [J].