Specificity, cross-reactivity, and function of antibodies elicited by Zika virus infection

被引：613

作者：

Stettler, Karin ^{[1
]}

Beltramello, Martina ^{[1
]}

Espinosa, Diego A. ^{[2
]}

Graham, Victoria ^{[3
]}

Cassotta, Antonino ^{[4
,5
]}

Bianchi, Siro ^{[1
]}

Vanzetta, Fabrizia ^{[1
]}

Minola, Andrea ^{[1
]}

Jaconi, Stefano ^{[1
]}

Mele, Federico

Foglierini, Mathilde ^{[4
]}

Pedotti, Mattia ^{[4
]}

Simonelli, Luca ^{[4
]}

Dowall, Stuart ^{[3
]}

Atkinson, Barry ^{[3
]}

Percivalle, Elena ^{[6
]}

Simmons, Cameron P. ^{[7
,8
,9
]}

Varani, Luca ^{[4
]}

Blum, Johannes ^{[10
,11
]}

Baldanti, Fausto ^{[6
]}

Cameroni, Elisabetta ^{[1
]}

Hewson, Roger

Harris, Eva ^{[2
]}

Lanzavecchia, Antonio ^{[4
,5
]}

Sallusto, Federica ^{[4
]}

Corti, Davide ^{[1
]}

机构：

[1] Humabs BioMed SA, Via Mirasole 1, CH-6500 Bellinzona, Switzerland

[2] Univ Calif Berkeley, Sch Publ Hlth, Div Infect Dis & Vaccinol, Berkeley, CA USA

[3] Publ Hlth England, Natl Infect Serv, Salisbury, Wilts, England

[4] Univ Svizzera Italiana, Inst Res Biomed, Via Vincenzo Vela 6, CH-6500 Bellinzona, Switzerland

[5] ETH, Inst Microbiol, Wolfgang Pauli Str 10, CH-8093 Zurich, Switzerland

[6] Fdn Ist Ricovero & Cura Carattere Sci IRCCS, Policlin San Matteo, Microbiol & Virol Dept, Mol Virol Unit, Pavia, Italy

[7] Univ Oxford, Nuffield Dept Med, Ctr Trop Med, Oxford OX1 2JD, England

[8] Univ Oxford, Clin Res Unit, Ctr Trop Med, Ho Chi Minh City, Vietnam

[9] Univ Melbourne, Peter Doherty Inst, Dept Microbiol & Immunol, 792 Elizabeth St, Melbourne, Vic 3000, Australia

[10] Swiss Trop & Publ Hlth Inst, Socinstr 57, CH-4002 Basel, Switzerland

[11] Univ Basel, Petersgraben 4, CH-4031 Basel, Switzerland

来源：

SCIENCE | 2016年 / 353卷 / 6301期

基金：

美国国家卫生研究院; 瑞士国家科学基金会; 欧洲研究理事会;

关键词：

DENGUE VIRUS; MONOCLONAL-ANTIBODIES; DETERMINANTS; ENHANCEMENT; EPITOPES; BINDING; FEVER; MODEL;

D O I：

10.1126/science.aaf8505

中图分类号：

O [数理科学和化学]; P [天文学、地球科学]; Q [生物科学]; N [自然科学总论];

学科分类号：

07 ; 0710 ; 09 ;

摘要：

Zika virus (ZIKV), a mosquito-borne flavivirus with homology to Dengue virus (DENV), has become a public health emergency. By characterizing memory lymphocytes from ZIKV-infected patients, we dissected ZIKV-specific and DENV-cross-reactive immune responses. Antibodies to nonstructural protein 1 (NS1) were largely ZIKV-specific and were used to develop a serological diagnostic tool. In contrast, antibodies against E protein domain I/II (EDI/II) were cross-reactive and, although poorly neutralizing, potently enhanced ZIKV and DENV infection in vitro and lethally enhanced DENV disease in mice. Memory T cells against NS1 or E proteins were poorly cross-reactive, even in donors preexposed to DENV. The most potent neutralizing antibodies were ZIKV-specific and targeted EDIII or quaternary epitopes on infectious virus. An EDIII-specific antibody protected mice from lethal ZIKV infection, illustrating the potential for antibody-based therapy.

引用

页码：823 / 826

页数：4

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