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

被引:612
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
基金
瑞士国家科学基金会; 美国国家卫生研究院; 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
收藏
页码:823 / 826
页数:4
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