title: Human antibody responses after dengue virus infection are highly cross-reactive to Zika virus.
abstract: Zika virus (ZIKV) is an emerging mosquito-borne flavivirus of significant public health concern. ZIKV shares a high degree of sequence and structural homology compared with other flaviviruses, including dengue virus (DENV), resulting in immunological cross-reactivity. Improving our current understanding of the extent and characteristics of this immunological cross-reactivity is important, as ZIKV is presently circulating in areas that are highly endemic for dengue. To assess the magnitude and functional quality of cross-reactive immune responses between these closely related viruses, we tested acute and convalescent sera from nine Thai patients with PCR-confirmed DENV infection against ZIKV. All of the sera tested were cross-reactive with ZIKV, both in binding and in neutralization. To deconstruct the observed serum cross-reactivity in depth, we also characterized a panel of DENV-specific plasmablast-derived monoclonal antibodies (mAbs) for activity against ZIKV. Nearly half of the 47 DENV-reactive mAbs studied bound to both whole ZIKV virion and ZIKV lysate, of which a subset also neutralized ZIKV. In addition, both sera and mAbs from the dengue-infected patients enhanced ZIKV infection of Fc gamma receptor (FcγR)-bearing cells in vitro. Taken together, these findings suggest that preexisting immunity to DENV may impact protective immune responses against ZIKV. In addition, the extensive cross-reactivity may have implications for ZIKV virulence and disease severity in DENV-experienced populations.
authors.affiliation: Emory Vaccine Center, Emory University School of Medicine, Atlanta, GA 30322; Division of Infectious Disease, Department of Pediatrics, Emory University School of Medicine, Atlanta, GA 30322;
authors.forename: Lalita
authors.initials: L
authors.lastname: Priyamvada
authors.affiliation: Emory Vaccine Center, Emory University School of Medicine, Atlanta, GA 30322; Division of Infectious Disease, Department of Pediatrics, Emory University School of Medicine, Atlanta, GA 30322;
authors.forename: Kendra M
authors.initials: KM
authors.lastname: Quicke
authors.affiliation: Emory Vaccine Center, Emory University School of Medicine, Atlanta, GA 30322; Department of Microbiology and Immunology, Emory University School of Medicine, Atlanta, GA 30322;
authors.forename: William H
authors.initials: WH
authors.lastname: Hudson
authors.affiliation: Department of Research and Development, Faculty of Medicine Siriraj Hospital, Mahidol University, Bangkok 10700, Thailand;
authors.forename: Nattawat
authors.initials: N
authors.lastname: Onlamoon
authors.affiliation: Emory Vaccine Center, Emory University School of Medicine, Atlanta, GA 30322; Department of Microbiology and Immunology, Emory University School of Medicine, Atlanta, GA 30322; Department of Microbiology, Faculty of Medicine Siriraj Hospital, Mahidol University, Bangkok 10700, Thailand;
authors.forename: Jaturong
authors.initials: J
authors.lastname: Sewatanon
authors.affiliation: The Hope Clinic of the Emory Vaccine Center, Emory University School of Medicine, Atlanta, GA 30322; Department of Medicine, Division of Infectious Diseases, Emory University School of Medicine, Atlanta, GA 30322;
authors.forename: Srilatha
authors.initials: S
authors.lastname: Edupuganti
authors.affiliation: Department of Research and Development, Faculty of Medicine Siriraj Hospital, Mahidol University, Bangkok 10700, Thailand;
authors.forename: Kovit
authors.initials: K
authors.lastname: Pattanapanyasat
authors.affiliation: Department of Pediatrics, Faculty of Medicine Siriraj Hospital, Mahidol University, Bangkok 10700, Thailand;
authors.forename: Kulkanya
authors.initials: K
authors.lastname: Chokephaibulkit
authors.affiliation: The Hope Clinic of the Emory Vaccine Center, Emory University School of Medicine, Atlanta, GA 30322; Department of Medicine, Division of Infectious Diseases, Emory University School of Medicine, Atlanta, GA 30322;
authors.forename: Mark J
authors.initials: MJ
authors.lastname: Mulligan
authors.affiliation: Section of Rheumatology, The Knapp Center for Lupus and Immunology Research, Department of Medicine, University of Chicago, Chicago, IL 60637.
authors.forename: Patrick C
authors.initials: PC
authors.lastname: Wilson
authors.affiliation: Emory Vaccine Center, Emory University School of Medicine, Atlanta, GA 30322; Department of Microbiology and Immunology, Emory University School of Medicine, Atlanta, GA 30322; jwramme@emory.edu rahmed@emory.edu.
authors.forename: Rafi
authors.initials: R
authors.lastname: Ahmed
authors.affiliation: Emory Vaccine Center, Emory University School of Medicine, Atlanta, GA 30322; Division of Infectious Disease, Department of Pediatrics, Emory University School of Medicine, Atlanta, GA 30322;
authors.forename: Mehul S
authors.initials: MS
authors.lastname: Suthar
authors.affiliation: Emory Vaccine Center, Emory University School of Medicine, Atlanta, GA 30322; Division of Infectious Disease, Department of Pediatrics, Emory University School of Medicine, Atlanta, GA 30322; jwramme@emory.edu rahmed@emory.edu.
authors.forename: Jens
authors.initials: J
authors.lastname: Wrammert
mesh_terms: D000595:Amino Acid Sequence; D000818:Animals; D000917:Antibody Formation; D002522:Chlorocebus aethiops; D003429:Cross Reactions; D003715:Dengue / Q000276:immunology*; D003716:Dengue Virus / Q000276:immunology*; D006801:Humans; D009000:Monocytes / Q000821:virology; D009500:Neutralization Tests; D014709:Vero Cells; D014759:Viral Envelope Proteins / Q000737:chemistry / Q000276:immunology; D000071244:Zika Virus / Q000276:immunology*
chemical_list: D014759:Viral Envelope Proteins
keywords: B-cell responses; Zika virus; antibodies; cross-reactivity