Antibody-based assay discriminates Zika virus infection from other flaviviruses

Angel Balmaseda, Karin Stettler, Raquel Medialdea-Carrera, Damaris Collado, Xia Jin, José Victor Zambrana, Stefano Jaconi, Elisabetta Cameroni, Saira Saborio, Francesca Rovida, Elena Percivalle, Samreen Ijaz, Steve Dicks, Ines Ushiro-Lumb, Luisa Barzon, Patricia Siqueira, David W.G. Brown, Fausto Baldanti, Richard Tedder, Maria ZambonA. M. Bispo de Filippis, Eva Harris, Davide Corti

Research output: Contribution to journalArticle

Abstract

Zika virus (ZIKV) is a mosquito-borne flavivirus that emerged recently as a global health threat, causing a pandemic in the Americas. ZIKV infection mostly causes mild disease, but is linked to devastating congenital birth defects and Guillain-Barré syndrome in adults. The high level of cross-reactivity among flaviviruses and their cocirculation has complicated serological approaches to differentially detect ZIKV and dengue virus (DENV) infections, accentuating the urgent need for a specific and sensitive serological test. We previously generated a ZIKV nonstructural protein 1 (NS1)-specific human monoclonal antibody, which we used to develop an NS1-based competition ELISA. Well-characterized samples from RT-PCR-confirmed patients with Zika and individuals exposed to other flavivirus infections or vaccination were used in a comprehensive analysis to determine the sensitivity and specificity of the NS1 blockade-of-binding (BOB) assay, which was established in laboratories in five countries (Nicaragua, Brazil, Italy, United Kingdom, and Switzerland). Of 158 sera/ plasma from RT-PCR-confirmed ZIKV infections, 145 (91.8%) yielded greater than 50% inhibition. Of 171 patients with primary or secondary DENV infections, 152 (88.9%) scored negative. When the control group was extended to patients infected by other flaviviruses, other viruses, or healthy donors (n = 540), the specificity was 95.9%. We also analyzed longitudinal samples from DENV-immune and DENV-naive ZIKV infections and found inhibition was achieved within 10 d postonset of illness and maintained over time. Thus, the Zika NS1 BOB assay is sensitive, specific, robust, simple, low-cost, and accessible, and can detect recent and past ZIKV infections for surveillance, seroprevalence studies, and intervention trials.

Original languageEnglish
Pages (from-to)8384-8389
Number of pages6
JournalProceedings of the National Academy of Sciences of the United States of America
Volume114
Issue number31
DOIs
Publication statusPublished - Aug 1 2017

Keywords

  • dengue
  • ELISA
  • flaviviruses
  • serology
  • Zika

ASJC Scopus subject areas

  • General

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  • Cite this

    Balmaseda, A., Stettler, K., Medialdea-Carrera, R., Collado, D., Jin, X., Zambrana, J. V., Jaconi, S., Cameroni, E., Saborio, S., Rovida, F., Percivalle, E., Ijaz, S., Dicks, S., Ushiro-Lumb, I., Barzon, L., Siqueira, P., Brown, D. W. G., Baldanti, F., Tedder, R., ... Corti, D. (2017). Antibody-based assay discriminates Zika virus infection from other flaviviruses. Proceedings of the National Academy of Sciences of the United States of America, 114(31), 8384-8389. https://doi.org/10.1073/pnas.1704984114