3 years ago

Antibody-based assay discriminates Zika virus infection from other flaviviruses [Microbiology]

Antibody-based assay discriminates Zika virus infection from other flaviviruses [Microbiology]
Luisa Barzon, Elena Percivalle, Francesca Rovida, A. M. Bispo de Filippis, Richard Tedder, Karin Stettler, Davide Corti, Patricia Siqueira, Saira Saborio, Stefano Jaconi, Xia Jin, Damaris Collado, Ines Ushiro–Lumb, Steve Dicks, Angel Balmaseda, Eva Harris, Samreen Iȷaz, Elisabetta Cameroni, Raquel Medialdea–Carrera, Fausto Baldanti, David W. G. Brown, Maria Zambon, Jose Victor Zambrana

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.

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