title: A Multiplex Microsphere Immunoassay for Zika Virus Diagnosis.
abstract: Rapid and accurate diagnosis of infectious agents is essential for patient care, disease control, and countermeasure development. The present serologic diagnosis of Zika virus (ZIKV) infection relies mainly on IgM-capture ELISA which is confounded with the flaw of cross-reactivity among different flaviviruses. In this communication, we report a multiplex microsphere immunoassay (MIA) that captures the diagnostic power of viral envelope protein (that elicits robust, yet cross-reactive antibodies to other flaviviruses) and the differential power of viral nonstructural proteins NS1 and NS5 (that induce more virus-type specific antibodies). Using 153 patient specimens with known ZIKV and/or dengue virus (DENV; a closely related flavivirus) infections, we showed that (i) ZIKV envelope-based MIA is equivalent or more sensitive than IgM-capture ELISA in diagnosing ZIKV infection, (ii) antibody responses to NS1 and NS5 proteins are more ZIKV-specific than antibody response to envelope protein, (iii) inclusion of NS1 and NS5 in the MIA improves the diagnostic accuracy when compared with the MIA that uses envelope protein alone. The multiplex MIA achieves a rapid diagnosis (turnaround time<4h) and requires small specimen volume (10μl) in a single reaction. This serologic assay could be developed for use in clinical diagnosis of ZIKV infection and for monitoring immune responses in vaccine trials.
authors.affiliation: Wadsworth Center, New York State Department of Health, Albany, New York, USA. Electronic address: susan.wong@health.ny.gov.
authors.forename: Susan J
authors.initials: SJ
authors.lastname: Wong
authors.affiliation: Wadsworth Center, New York State Department of Health, Albany, New York, USA.
authors.forename: Andrea
authors.initials: A
authors.lastname: Furuya
authors.affiliation: Department of Biochemistry & Molecular Biology, University of Texas Medical Branch, Galveston, TX, USA.
authors.forename: Jing
authors.initials: J
authors.lastname: Zou
authors.affiliation: Department of Biochemistry & Molecular Biology, University of Texas Medical Branch, Galveston, TX, USA.
authors.forename: Xuping
authors.initials: X
authors.lastname: Xie
authors.affiliation: Wadsworth Center, New York State Department of Health, Albany, New York, USA.
authors.forename: Alan P
authors.initials: AP
authors.lastname: Dupuis
authors.affiliation: Wadsworth Center, New York State Department of Health, Albany, New York, USA.
authors.forename: Laura D
authors.initials: LD
authors.lastname: Kramer
authors.affiliation: Department of Biochemistry & Molecular Biology, University of Texas Medical Branch, Galveston, TX, USA; Department of Pharmacology & Toxicology, University of Texas Medical Branch, Galveston, TX, USA; Sealy Center for Structural Biology & Molecular Biophysics, University of Texas Medical Branch, Galveston, TX, USA; Institute for Translational Science, University of Texas Medical Branch, Galveston, TX, USA. Electronic address: peshi@utmb.edu.
authors.forename: Pei-Yong
authors.initials: PY
authors.lastname: Shi
mesh_terms: D000818:Animals; D000914:Antibodies, Viral / Q000097:blood / Q000276:immunology; D002522:Chlorocebus aethiops; D003429:Cross Reactions / Q000276:immunology; D003715:Dengue / Q000276:immunology / Q000821:virology; D003716:Dengue Virus / Q000276:immunology / Q000502:physiology; D004797:Enzyme-Linked Immunosorbent Assay / Q000379:methods; D054884:Host-Pathogen Interactions / Q000276:immunology; D006801:Humans; D007118:Immunoassay / Q000379:methods*; D008863:Microspheres; D015203:Reproducibility of Results; D012680:Sensitivity and Specificity; D014709:Vero Cells; D014759:Viral Envelope Proteins / Q000276:immunology; D017361:Viral Nonstructural Proteins / Q000276:immunology; D000071244:Zika Virus / Q000276:immunology* / Q000502:physiology; D000071243:Zika Virus Infection / Q000175:diagnosis* / Q000276:immunology / Q000821:virology
chemical_list: D000914:Antibodies, Viral; D014759:Viral Envelope Proteins; D017361:Viral Nonstructural Proteins
keywords: Diagnosis; Multiplex microsphere immunoassay; Serologic assay; Zika virus