Specificity, cross-reactivity, and function of antibodies elicited by Zika virus infection
Karin Stettlera✉, Martina Beltramelloa✉, Diego A. Espinosab, Victoria Grahamc, Antonino Cassottad e, Siro Bianchia, Fabrizia Zattaa, Andrea Minolaa, Stefano Jaconia, Federico Melee, Mathilde Foglierinie, Mattia Pedottie, Luca Simonellie, Stuart Dowallc, Barry Atkinsonc, Elena Percivallef, Cameron Paul Simmonsg h i, Luca Varanie, Johannes A. Blumj k, Fausto Baldantif, Elisabetta Cameronia, Roger Hewsonc, Eva Harrisb, Antonio Lanzavecchiad e, Federica Sallustoe, Davide Cortia
- aHumabs BioMed SA, Via Mirasole 1, 6500 Bellinzona, Switzerland
- bDivision of Infectious Diseases and Vaccinology, School of Public Health, University of California, Berkeley, Berkeley, CA, USA
- cNational Infection Service, Public Health England, Porton Down, Salisbury, Wiltshire, UK
- dInstitute for Microbiology, ETH Zurich, Wolfgang-Pauli-Strasse 10, 8093 Zurich, Switzerland
- eInstitute for Research in Biomedicine, Università della Svizzera italiana, Via Vincenzo Vela 6, 6500 Bellinzona, Switzerland
- fMolecular Virology Unit, Microbiology and Virology Department, Fondazione Istituto di Ricovero e Cura a Carattere Scientifico (IRCCS) Policlinico San Matteo, Pavia, Italy
- gCentre for Tropical Medicine, Nuffield Department of Medicine, University of Oxford, UK
- hDepartment of Microbiology and Immunology, University of Melbourne, Peter Doherty Institute, 792 Elizabeth Street, Melbourne VIC 3000, Australia
- iOxford University Clinical Research Unit, Center for Tropical Medicine, Ho Chi Minh City, Vietnam
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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 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.