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 journalArticle

Abstract

Zika virus (ZIKV), a mosquito-borne flavivirus with homology to Dengue virus (DENV), has become a public health emergency. By characterizing memory cells from ZIKV-infected patients, we dissected ZIKV-specific and DENV-crossreactive immune responses. Antibodies to 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, while 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 crossreactive, even in donors pre-exposed 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 languageEnglish
Pages (from-to)1-9
Number of pages9
JournalScience
DOIs
Publication statusAccepted/In press - Jul 14 2016

ASJC Scopus subject areas

  • Medicine(all)
  • General

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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. (Accepted/In press). Specificity, cross-reactivity and function of antibodies elicited by Zika virus infection. Science, 1-9. https://doi.org/10.1126/science.aaf8505