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

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[h=1][/h] Specificity, cross-reactivity and function of antibodies elicited by Zika virus infection

• Karin Stettler[SUP]1[/SUP],*,
• Martina Beltramello[SUP]1[/SUP],*,
• Diego A. Espinosa[SUP]2[/SUP],?,
• Victoria Graham[SUP]3[/SUP],?,
• Antonino Cassotta[SUP]4[/SUP],[SUP]5[/SUP],?,
• Siro Bianchi[SUP]1[/SUP],?,
• Fabrizia Vanzetta[SUP]1[/SUP],?,
• Andrea Minola[SUP]1[/SUP],
• Stefano Jaconi[SUP]1[/SUP],
• Federico Mele[SUP]4[/SUP],
• Mathilde Foglierini[SUP]4[/SUP],
• Mattia Pedotti[SUP]4[/SUP],
• Luca Simonelli[SUP]4[/SUP],
• Stuart Dowall[SUP]3[/SUP],
• Barry Atkinson[SUP]3[/SUP],
• Elena Percivalle[SUP]6[/SUP],
• Cameron P. Simmons[SUP]7[/SUP],[SUP]8[/SUP],
• Luca Varani[SUP]4[/SUP],
• Johannes Blum[SUP]9[/SUP],[SUP]10[/SUP],
• Fausto Baldanti[SUP]6[/SUP],
• Elisabetta Cameroni[SUP]1[/SUP],
• Roger Hewson[SUP]3[/SUP],
• Eva Harris[SUP]2[/SUP],
• Antonio Lanzavecchia[SUP]4[/SUP],[SUP]5[/SUP],
• Federica Sallusto[SUP]4[/SUP],?,?,
• Davide Corti[SUP]1[/SUP],?,?

• [SUP]1[/SUP]Humabs BioMed SA, Via Mirasole 1, 6500 Bellinzona, Switzerland.
• [SUP]2[/SUP]Division of Infectious Diseases and Vaccinology, School of Public Health, University of California, Berkeley, Berkeley, CA, USA.
• [SUP]3[/SUP]National Infection Service, Public Health England, Porton Down, Salisbury, Wiltshire, UK.
• [SUP]4[/SUP]Insitute for Research in Biomedicine, Universit? della Svizzera italiana, Via Vincenzo Vela 6, 6500 Bellinzona, Switzerland.
• [SUP]5[/SUP]Insitute for Microbiology, ETH Zurich, Wolfgang-Pauli-Strasse 10, 8093 Zurich, Switzerland.
• [SUP]6[/SUP]Molecular Virology Unit, Microbiology and Virology Department, Fondazione IRCCS Policlinico San Matteo, Pavia, Italy.
• [SUP]7[/SUP]Centre for Tropical Medicine, Nuffield Department of Medicine, University of Oxford, UK Oxford University Clinical Research Unit, Center for Tropical Medicine, Ho Chi Minh City, Vietnam.
• [SUP]8[/SUP]Department of Microbiology and Immunology, University of Melbourne, Peter Doherty Institute, Australia.
• [SUP]9[/SUP]Swiss Tropical and Public Health Institute, Socinstrasse 57, 4002 Basel, Switzerland.
• [SUP]10[/SUP]University of Basel, Petersgraben 4, 4031 Basel, Switzerland.

• ↵?Corresponding author. Email: davide.corti{at}humabs.ch (D.C.); federica.sallusto{at}irb.usi.ch (F.S.)

• ↵* These authors contributed equally to this work.
• ↵? These authors contributed equally to this work.
• ↵? These authors contributed equally to this work.

Science 14 Jul 2016:

DOI: 10.1126/science.aaf8505
[h=2]Abstract[/h] 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.

full text


http://science.sciencemag.org/content/early/2016/07/13/science.aaf8505.full