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 language | English |
|---|---|
| Pages (from-to) | 8384-8389 |
| Number of pages | 6 |
| Journal | Proceedings of the National Academy of Sciences of the United States of America |
| Volume | 114 |
| Issue number | 31 |
| DOIs | |
| Publication status | Published - 1 Aug 2017 |
Bibliographical note
Funding Information:We thank past and present members of the study team based at the Centro de Salud S?crates Flores Vivas, Hospital Infantil Manuel de Jes?s Rivera, the National Virology Laboratory in the Centro Nacional de Diagn?stico y Referencia, and the Sustainable Sciences Institute in Nicaragua for their dedication and high-quality work, as well as the children who participated in the studies and their families. We thank the Flavivirus Laboratory, the Influenza Laboratory, and the Viral Hepatitis Laboratory from Fiocruz and the Evandro Chagas National Institute of Infectious diseases for providing the samples from Brazil. We thank the staff of the Rare and Imported Disease Laboratory at Public Health England (PHE) in Porton Down, the staff of virus and bacterial reference divisions at PHE Colindale for technical assistance, and particularly Dr. Jennifer Tossiwil, Dr. Colin Brown, Dr. Tim Brooks, and Dr. Emma Aarons for their assistance. Partial funding support was provided by National Institutes of Health Grants P01AI106695 (to E.H.), U19AI118610 (to E.H.), and R01AI099631 (to A.B.). R.M.-C.?s work is supported by the National Institute for Health Research (Health Protection Research Unit) in Emerging and Zoonotic Infections at the University of Liverpool in partnership with PHE and Liverpool School of Tropical Medicine. This work was also supported by Medical Research Council ?Rapid response to Zika virus? Grant MC_PC_15093.
Keywords
- ELISA
- Zika
- dengue
- flaviviruses
- serology
