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 journalArticleResearchpeer-review

594 Citations (Scopus)


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 languageEnglish
Pages (from-to)823-826
Number of pages4
Issue number6301
Publication statusPublished - 19 Aug 2016
Externally publishedYes

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