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Compensating for cross-reactions using avidity and computation in a suspension multiplex immunoassay for serotyping of Zika versus other flavivirus infections
Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Biochemistry and Microbiology. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Clinical Microbiology.
Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Biochemistry and Microbiology. Univ Uppsala Hosp, Lab Clin Microbiol, Uppsala, Sweden..
Univ Helsinki, Dept Vet Biosci & Virol, Helsinki, Finland.;Helsinki Univ Hosp, Helsinki, Finland..
Bernhard Nocht Inst Trop Med, WHO Collaborating Ctr Arbovirus & Haemorrhag Feve, D-20359 Hamburg, Germany.;Univ Rostock, Dept Trop Med & Infect Dis, Ctr Internal Med 2, D-18057 Rostock, Germany..
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2017 (English)In: Medical Microbiology and Immmunology, ISSN 0300-8584, E-ISSN 1432-1831, Vol. 206, no 5, p. 383-401Article in journal (Refereed) Published
Abstract [en]

The recent spread of Zika virus (ZIKV) in the Americas and Asia necessitates an increased preparedness for improved maternal and perinatal health and blood safety. However, serological cross-reactions, especially to Dengue virus (DENV), complicate ZIKV antibody serodiagnosis. A novel "pan-Flavi" suspension multiplex immunoassay (PFSMIA) using 25 antigens, whole virus (WV), non-structural protein 1 (NS1), and envelope (E) proteins, from 7 zoonotic flaviviruses for specific detection of ZIKV and DENV IgM and IgG was developed. Patterns of antibody cross-reactivity, avidity, and kinetics were established in 104 sera from returning travelers with known ZIKV and DENV infections. PFSMIA gave IgM- and IgG-sensitivities for both viruses of 96-100%, compared to an immunofluorescence assay. Main IgM cross-reactions were to NS1, for IgG to the E and WV antigens. Infecting virus yielded reactivity to several antigens of the homologous virus, while cross-reactions tended to occur only to a single antigen from heterologous virus(es). A specificity-enhancing computer procedure took into account antibody isotype, number of antibody-reactive antigens per virus, avidity, average degree of cross-reactivity to heterologous flavivirus antigens, and reactivity changes in serial sera. It classified all 50 cases correctly. Applied to sera from 200 pregnant women and 173 blood donors from Sweden, one blood donor was found ZIKV NS1 IgM positive, and another as ZIKV NS1 IgG positive. These samples did not react with other ZIKV antigens and were thereby judged as false-positives. PFSMIA provided sensitive and specific ZIKV and DENV serology, warranting high-throughput serological surveillance and a minimized need for laborious and expensive virus neutralization assays.

Place, publisher, year, edition, pages
SPRINGER , 2017. Vol. 206, no 5, p. 383-401
Keyword [en]
Zika virus, Dengue virus, Flavivirus, Suspension multiplex immunoassay, Serological crossreaction, Pathogen surveillance
National Category
Medical and Health Sciences
Identifiers
URN: urn:nbn:se:uu:diva-335127DOI: 10.1007/s00430-017-0517-yISI: 000410805500006PubMedID: 28852878OAI: oai:DiVA.org:uu-335127DiVA, id: diva2:1162263
Available from: 2017-12-04 Created: 2017-12-04 Last updated: 2017-12-04Bibliographically approved

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