title: Specificity, cross-reactivity, and function of antibodies elicited by Zika virus infection.
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.
authors.affiliation: Humabs BioMed SA, Via Mirasole 1, 6500 Bellinzona, Switzerland.
authors.forename: Karin
authors.initials: K
authors.lastname: Stettler
authors.affiliation: Humabs BioMed SA, Via Mirasole 1, 6500 Bellinzona, Switzerland.
authors.forename: Martina
authors.initials: M
authors.lastname: Beltramello
authors.affiliation: Division of Infectious Diseases and Vaccinology, School of Public Health, University of California, Berkeley, Berkeley, CA, USA.
authors.forename: Diego A
authors.initials: DA
authors.lastname: Espinosa
authors.affiliation: National Infection Service, Public Health England, Porton Down, Salisbury, Wiltshire, UK.
authors.forename: Victoria
authors.initials: V
authors.lastname: Graham
authors.affiliation: Institute for Research in Biomedicine, Università della Svizzera italiana, Via Vincenzo Vela 6, 6500 Bellinzona, Switzerland. Institute for Microbiology, ETH Zurich, Wolfgang-Pauli-Strasse 10, 8093 Zurich, Switzerland.
authors.forename: Antonino
authors.initials: A
authors.lastname: Cassotta
authors.affiliation: Humabs BioMed SA, Via Mirasole 1, 6500 Bellinzona, Switzerland.
authors.forename: Siro
authors.initials: S
authors.lastname: Bianchi
authors.affiliation: Humabs BioMed SA, Via Mirasole 1, 6500 Bellinzona, Switzerland.
authors.forename: Fabrizia
authors.initials: F
authors.lastname: Vanzetta
authors.affiliation: Humabs BioMed SA, Via Mirasole 1, 6500 Bellinzona, Switzerland.
authors.forename: Andrea
authors.initials: A
authors.lastname: Minola
authors.affiliation: Humabs BioMed SA, Via Mirasole 1, 6500 Bellinzona, Switzerland.
authors.forename: Stefano
authors.initials: S
authors.lastname: Jaconi
authors.affiliation: Institute for Research in Biomedicine, Università della Svizzera italiana, Via Vincenzo Vela 6, 6500 Bellinzona, Switzerland.
authors.forename: Federico
authors.initials: F
authors.lastname: Mele
authors.affiliation: Institute for Research in Biomedicine, Università della Svizzera italiana, Via Vincenzo Vela 6, 6500 Bellinzona, Switzerland.
authors.forename: Mathilde
authors.initials: M
authors.lastname: Foglierini
authors.affiliation: Institute for Research in Biomedicine, Università della Svizzera italiana, Via Vincenzo Vela 6, 6500 Bellinzona, Switzerland.
authors.forename: Mattia
authors.initials: M
authors.lastname: Pedotti
authors.affiliation: Institute for Research in Biomedicine, Università della Svizzera italiana, Via Vincenzo Vela 6, 6500 Bellinzona, Switzerland.
authors.forename: Luca
authors.initials: L
authors.lastname: Simonelli
authors.affiliation: National Infection Service, Public Health England, Porton Down, Salisbury, Wiltshire, UK.
authors.forename: Stuart
authors.initials: S
authors.lastname: Dowall
authors.affiliation: National Infection Service, Public Health England, Porton Down, Salisbury, Wiltshire, UK.
authors.forename: Barry
authors.initials: B
authors.lastname: Atkinson
authors.affiliation: Molecular Virology Unit, Microbiology and Virology Department, Fondazione Istituto di Ricovero e Cura a Carattere Scientifico (IRCCS) Policlinico San Matteo, Pavia, Italy.
authors.forename: Elena
authors.initials: E
authors.lastname: Percivalle
authors.affiliation: 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. Department of Microbiology and Immunology, University of Melbourne, Peter Doherty Institute, 792 Elizabeth Street, Melbourne VIC 3000, Australia.
authors.forename: Cameron P
authors.initials: CP
authors.lastname: Simmons
authors.affiliation: Institute for Research in Biomedicine, Università della Svizzera italiana, Via Vincenzo Vela 6, 6500 Bellinzona, Switzerland.
authors.forename: Luca
authors.initials: L
authors.lastname: Varani
authors.affiliation: Swiss Tropical and Public Health Institute, Socinstrasse 57, 4002 Basel, Switzerland. University of Basel, Petersgraben 4, 4031 Basel, Switzerland.
authors.forename: Johannes
authors.initials: J
authors.lastname: Blum
authors.affiliation: Molecular Virology Unit, Microbiology and Virology Department, Fondazione Istituto di Ricovero e Cura a Carattere Scientifico (IRCCS) Policlinico San Matteo, Pavia, Italy.
authors.forename: Fausto
authors.initials: F
authors.lastname: Baldanti
authors.affiliation: Humabs BioMed SA, Via Mirasole 1, 6500 Bellinzona, Switzerland.
authors.forename: Elisabetta
authors.initials: E
authors.lastname: Cameroni
authors.affiliation: National Infection Service, Public Health England, Porton Down, Salisbury, Wiltshire, UK.
authors.forename: Roger
authors.initials: R
authors.lastname: Hewson
authors.affiliation: Division of Infectious Diseases and Vaccinology, School of Public Health, University of California, Berkeley, Berkeley, CA, USA.
authors.forename: Eva
authors.initials: E
authors.lastname: Harris
authors.affiliation: Institute for Research in Biomedicine, Università della Svizzera italiana, Via Vincenzo Vela 6, 6500 Bellinzona, Switzerland. Institute for Microbiology, ETH Zurich, Wolfgang-Pauli-Strasse 10, 8093 Zurich, Switzerland.
authors.forename: Antonio
authors.initials: A
authors.lastname: Lanzavecchia
authors.affiliation: Institute for Research in Biomedicine, Università della Svizzera italiana, Via Vincenzo Vela 6, 6500 Bellinzona, Switzerland. davide.corti@humabs.ch federica.sallusto@irb.usi.ch.
authors.forename: Federica
authors.initials: F
authors.lastname: Sallusto
authors.affiliation: Humabs BioMed SA, Via Mirasole 1, 6500 Bellinzona, Switzerland. davide.corti@humabs.ch federica.sallusto@irb.usi.ch.
authors.forename: Davide
authors.initials: D
authors.lastname: Corti
mesh_terms: D000818:Animals; D000911:Antibodies, Monoclonal / Q000737:chemistry / Q000276:immunology* / Q000627:therapeutic use; D057134:Antibodies, Neutralizing / Q000737:chemistry / Q000276:immunology* / Q000627:therapeutic use; D000914:Antibodies, Viral / Q000737:chemistry / Q000276:immunology* / Q000627:therapeutic use; D000918:Antibody Specificity; D003429:Cross Reactions; D003716:Dengue Virus / Q000276:immunology; D004195:Disease Models, Animal; D006801:Humans; D016056:Immunodominant Epitopes / Q000276:immunology; D007156:Immunologic Memory; D017434:Protein Structure, Tertiary; D013601:T-Lymphocytes / Q000276:immunology; D014759:Viral Envelope Proteins / Q000276:immunology; D017361:Viral Nonstructural Proteins / Q000276:immunology; D000071244:Zika Virus / Q000276:immunology*; D000071243:Zika Virus Infection / Q000276:immunology* / Q000517:prevention & control / Q000628:therapy
chemical_list: D000911:Antibodies, Monoclonal; D057134:Antibodies, Neutralizing; D000914:Antibodies, Viral; D016056:Immunodominant Epitopes; D014759:Viral Envelope Proteins; D017361:Viral Nonstructural Proteins