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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
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.
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页码:271 / 283
页数:13
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