Specificity, cross-reactivity, and function of antibodies elicited by Zika virus infection
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...
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| Published in | Science (American Association for the Advancement of Science) Vol. 353; no. 6301; pp. 823 - 826 |
|---|---|
| Main Authors | , , , , , , , , , , , , , , , , , , , , , , , , , |
| Format | Journal Article |
| Language | English |
| Published |
United States
American Association for the Advancement of Science
19.08.2016
The American Association for the Advancement of Science |
| Subjects | |
| Online Access | Get full text |
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| 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 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 l/ll (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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| AbstractList | 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 l/ll (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. Characterizing the Zika virus antibody responseGiven the public health emergency that Zika virus poses, scientists are seeking to understand the Zika-specific immune response. Stettler et al. analyzed 119 monoclonal antibodies isolated from four donors that were infected with Zika virus during the present epidemic, including two individuals that had previously been infected with dengue virus, another member of the flavivirus family. Neutralizing antibodies primarily recognized the envelope protein domain III (EDIII) or quaternary epitopes on the intact virus, and an EDIII-targeted antibody protected mice against lethal infection. Some EDI/II-targeting antibodies cross-reacted with dengue virus in vitro and could enhance disease in dengue-infected mice. Whether dengue and Zika virus antibodies cross-react in humans remains to be tested.Science, this issue p. 823 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. Given the public health emergency that Zika virus poses, scientists are seeking to understand the Zika-specific immune response. Stettler et al. analyzed 119 monoclonal antibodies isolated from four donors that were infected with Zika virus during the present epidemic, including two individuals that had previously been infected with dengue virus, another member of the flavivirus family. Neutralizing antibodies primarily recognized the envelope protein domain III (EDIII) or quaternary epitopes on the intact virus, and an EDIII-targeted antibody protected mice against lethal infection. Some EDI/II-targeting antibodies cross-reacted with dengue virus in vitro and could enhance disease in dengue-infected mice. Whether dengue and Zika virus antibodies cross-react in humans remains to be tested. Science, this issue p. 823 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. Given the public health emergency that Zika virus poses, scientists are seeking to understand the Zika-specific immune response. Stettler et al. analyzed 119 monoclonal antibodies isolated from four donors that were infected with Zika virus during the present epidemic, including two individuals that had previously been infected with dengue virus, another member of the flavivirus family. Neutralizing antibodies primarily recognized the envelope protein domain III (EDIII) or quaternary epitopes on the intact virus, and an EDIII-targeted antibody protected mice against lethal infection. Some EDI/II-targeting antibodies cross-reacted with dengue virus in vitro and could enhance disease in dengue-infected mice. Whether dengue and Zika virus antibodies cross-react in humans remains to be tested. Science , this issue p. 823 Cross-reactive antibody responses may pose a risk for disease on secondary infections with Dengue and/or Zika viruses. 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. 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. |
| Author | Lanzavecchia, Antonio Hewson, Roger Jaconi, Stefano Baldanti, Fausto Simonelli, Luca Percivalle, Elena Stettler, Karin Vanzetta, Fabrizia Espinosa, Diego A. Beltramello, Martina Bianchi, Siro Atkinson, Barry Varani, Luca Sallusto, Federica Simmons, Cameron P. Harris, Eva Foglierini, Mathilde Blum, Johannes Minola, Andrea Pedotti, Mattia Cameroni, Elisabetta Cassotta, Antonino Corti, Davide Graham, Victoria Mele, Federico Dowall, Stuart |
| Author_xml | – sequence: 1 givenname: Karin surname: Stettler fullname: Stettler, Karin – sequence: 2 givenname: Martina surname: Beltramello fullname: Beltramello, Martina – sequence: 3 givenname: Diego A. surname: Espinosa fullname: Espinosa, Diego A. – sequence: 4 givenname: Victoria surname: Graham fullname: Graham, Victoria – sequence: 5 givenname: Antonino surname: Cassotta fullname: Cassotta, Antonino – sequence: 6 givenname: Siro surname: Bianchi fullname: Bianchi, Siro – sequence: 7 givenname: Fabrizia surname: Vanzetta fullname: Vanzetta, Fabrizia – sequence: 8 givenname: Andrea surname: Minola fullname: Minola, Andrea – sequence: 9 givenname: Stefano surname: Jaconi fullname: Jaconi, Stefano – sequence: 10 givenname: Federico surname: Mele fullname: Mele, Federico – sequence: 11 givenname: Mathilde surname: Foglierini fullname: Foglierini, Mathilde – sequence: 12 givenname: Mattia surname: Pedotti fullname: Pedotti, Mattia – sequence: 13 givenname: Luca surname: Simonelli fullname: Simonelli, Luca – sequence: 14 givenname: Stuart surname: Dowall fullname: Dowall, Stuart – sequence: 15 givenname: Barry surname: Atkinson fullname: Atkinson, Barry – sequence: 16 givenname: Elena surname: Percivalle fullname: Percivalle, Elena – sequence: 17 givenname: Cameron P. surname: Simmons fullname: Simmons, Cameron P. – sequence: 18 givenname: Luca surname: Varani fullname: Varani, Luca – sequence: 19 givenname: Johannes surname: Blum fullname: Blum, Johannes – sequence: 20 givenname: Fausto surname: Baldanti fullname: Baldanti, Fausto – sequence: 21 givenname: Elisabetta surname: Cameroni fullname: Cameroni, Elisabetta – sequence: 22 givenname: Roger surname: Hewson fullname: Hewson, Roger – sequence: 23 givenname: Eva surname: Harris fullname: Harris, Eva – sequence: 24 givenname: Antonio surname: Lanzavecchia fullname: Lanzavecchia, Antonio – sequence: 25 givenname: Federica surname: Sallusto fullname: Sallusto, Federica – sequence: 26 givenname: Davide surname: Corti fullname: Corti, Davide |
| BackLink | https://www.ncbi.nlm.nih.gov/pubmed/27417494$$D View this record in MEDLINE/PubMed |
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| CODEN | SCIEAS |
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| Snippet | Zika virus (ZIKV), a mosquito-borne flavivirus with homology to Dengue virus (DENV), has become a public health emergency. By characterizing memory lymphocytes... Given the public health emergency that Zika virus poses, scientists are seeking to understand the Zika-specific immune response. Stettler et al. analyzed 119... Given the public health emergency that Zika virus poses, scientists are seeking to understand the Zika-specific immune response. Stettler et al. analyzed 119... Characterizing the Zika virus antibody responseGiven the public health emergency that Zika virus poses, scientists are seeking to understand the Zika-specific... |
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| SubjectTerms | Animals Antibodies Antibodies, Monoclonal - chemistry Antibodies, Monoclonal - immunology Antibodies, Monoclonal - therapeutic use Antibodies, Neutralizing - chemistry Antibodies, Neutralizing - immunology Antibodies, Neutralizing - therapeutic use Antibodies, Viral - chemistry Antibodies, Viral - immunology Antibodies, Viral - therapeutic use Antibody Specificity Cross Reactions Dengue fever Dengue virus Dengue Virus - immunology Disease Models, Animal Flavivirus Humans Immune response Immunodominant Epitopes - immunology Immunologic Memory In vitro testing Lymphocytes Mice Monoclonal antibodies Neutralizing Protein Structure, Tertiary Proteins Public health T-Lymphocytes - immunology Vector-borne diseases Viral diseases Viral Envelope Proteins - immunology Viral Nonstructural Proteins - immunology Viruses Zika virus Zika Virus - immunology Zika Virus Infection - immunology Zika Virus Infection - prevention & control Zika Virus Infection - therapy |
| Title | Specificity, cross-reactivity, and function of antibodies elicited by Zika virus infection |
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