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

Karin Stettler; Martina Beltramello; Diego A. Espinosa; Victoria Graham; Antonino Cassotta; Siro Bianchi; Fabrizia Vanzetta; Andrea Minola; Stefano Jaconi; Federico Mele; Mathilde Foglierini; Mattia Pedotti; Luca Simonelli; Stuart Dowall; Barry Atkinson; Elena Percivalle; Cameron P. Simmons; Luca Varani; Johannes Blum; Fausto Baldanti; Elisabetta Cameroni; Roger Hewson; Eva Harris; Antonio Lanzavecchia; Federica Sallusto; Davide Corti

doi:10.1126/science.aaf8505

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

Karin Stettler, Martina Beltramello, Diego A. Espinosa, Victoria Graham, Antonino Cassotta, Siro Bianchi, Fabrizia Vanzetta, Andrea Minola, Stefano Jaconi, Federico Mele, Mathilde Foglierini, Mattia Pedotti, Luca Simonelli, Stuart Dowall, Barry Atkinson, Elena Percivalle, Cameron P. Simmons, Luca Varani, Johannes Blum, Fausto BaldantiElisabetta Cameroni, Roger Hewson, Eva Harris, Antonio Lanzavecchia, Federica Sallusto, Davide Corti

Research output: Contribution to journal › Article › Research › peer-review

637 Citations (Scopus)

Abstract

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 DENVcross-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.

Original language	English
Pages (from-to)	823-826
Number of pages	4
Journal	Science
Volume	353
Issue number	6301
DOIs	https://doi.org/10.1126/science.aaf8505
Publication status	Published - 19 Aug 2016
Externally published	Yes

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Stettler, K., Beltramello, M., Espinosa, D. A., Graham, V., Cassotta, A., Bianchi, S., Vanzetta, F., Minola, A., Jaconi, S., Mele, F., Foglierini, M., Pedotti, M., Simonelli, L., Dowall, S., Atkinson, B., Percivalle, E., Simmons, C. P., Varani, L., Blum, J., ... Corti, D. (2016). Specificity, cross-reactivity, and function of antibodies elicited by Zika virus infection. Science, 353(6301), 823-826. https://doi.org/10.1126/science.aaf8505

@article{2b54ad9e390041b5b3f64dbbad4aefe0,

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

abstract = "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 DENVcross-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.",

author = "Karin Stettler and Martina Beltramello and Espinosa, {Diego A.} and Victoria Graham and Antonino Cassotta and Siro Bianchi and Fabrizia Vanzetta and Andrea Minola and Stefano Jaconi and Federico Mele and Mathilde Foglierini and Mattia Pedotti and Luca Simonelli and Stuart Dowall and Barry Atkinson and Elena Percivalle and Simmons, {Cameron P.} and Luca Varani and Johannes Blum and Fausto Baldanti and Elisabetta Cameroni and Roger Hewson and Eva Harris and Antonio Lanzavecchia and Federica Sallusto and Davide Corti",

year = "2016",

month = aug,

day = "19",

doi = "10.1126/science.aaf8505",

language = "English",

volume = "353",

pages = "823--826",

journal = "Science",

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Stettler, K, Beltramello, M, Espinosa, DA, Graham, V, Cassotta, A, Bianchi, S, Vanzetta, F, Minola, A, Jaconi, S, Mele, F, Foglierini, M, Pedotti, M, Simonelli, L, Dowall, S, Atkinson, B, Percivalle, E, Simmons, CP, Varani, L, Blum, J, Baldanti, F, Cameroni, E, Hewson, R, Harris, E, Lanzavecchia, A, Sallusto, F & Corti, D 2016, 'Specificity, cross-reactivity, and function of antibodies elicited by Zika virus infection', Science, vol. 353, no. 6301, pp. 823-826. https://doi.org/10.1126/science.aaf8505

TY - JOUR

T1 - Specificity, cross-reactivity, and function of antibodies elicited by Zika virus infection

AU - Stettler, Karin

AU - Beltramello, Martina

AU - Espinosa, Diego A.

AU - Graham, Victoria

AU - Cassotta, Antonino

AU - Bianchi, Siro

AU - Vanzetta, Fabrizia

AU - Minola, Andrea

AU - Jaconi, Stefano

AU - Mele, Federico

AU - Foglierini, Mathilde

AU - Pedotti, Mattia

AU - Simonelli, Luca

AU - Dowall, Stuart

AU - Atkinson, Barry

AU - Percivalle, Elena

AU - Simmons, Cameron P.

AU - Varani, Luca

AU - Blum, Johannes

AU - Baldanti, Fausto

AU - Cameroni, Elisabetta

AU - Hewson, Roger

AU - Harris, Eva

AU - Lanzavecchia, Antonio

AU - Sallusto, Federica

AU - Corti, Davide

PY - 2016/8/19

Y1 - 2016/8/19

N2 - 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 DENVcross-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.

AB - 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 DENVcross-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.

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U2 - 10.1126/science.aaf8505

DO - 10.1126/science.aaf8505

M3 - Article

AN - SCOPUS:84978910758

SN - 0036-8075

VL - 353

SP - 823

EP - 826

JO - Science

JF - Science

IS - 6301

ER -

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

Abstract

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