Development and evaluation of a novel high-throughput image-based fluorescent neutralization test for detection of Zika virus infection

• Published in: PLoS neglected tropical diseases Vol. 12; no. 3; p. e0006342
• Main Authors: Koishi, Andrea Cristine, Suzukawa, Andréia Akemi, Zanluca, Camila, Camacho, Daria Elena, Comach, Guillermo, Duarte Dos Santos, Claudia Nunes
• Format: Journal Article
• Language: English
• Published: United States Public Library of Science 15-03-2018; Public Library of Science (PLoS)
• Subjects: Abnormalities; Biology and life sciences; Brain; Clinical trials; Cross-reactivity; Dengue; Dengue fever; Dengue virus; Detection; Diagnosis; Disease control; ELISA; Enzyme-linked immunosorbent assay; Evaluation; Fever; Flavivirus; Fluorescence; Funding; Guillain-Barre syndrome; Health aspects; Human diseases; Image detection; Immunoglobulins; Infants; Infections; Malformations; Medical research; Medical tests; Medicine and Health Sciences; Neutralization; Newborn babies; Nucleic acids; Prevention; Public health; Research and Analysis Methods; Ribonucleic acid; RNA; Samples; Serological tests; Serology; Symptoms; Tropical diseases; Vaccines; Vector-borne diseases; Viral diseases; Viruses; Womens health; Yellow fever; Zika virus; Zika virus infection; Brazil; Venezuela
• ISSN: 1935-2735; 1935-2727; 1935-2735
• DOI: 10.1371/journal.pntd.0006342

Zika virus (ZIKV) is an emerging arbovirus belonging to the genus flavivirus that comprises other important public health viruses, such as dengue (DENV) and yellow fever (YFV). In general, ZIKV infection is a self-limiting disease, however cases of Guillain-Barré syndrome and congenital brain abnormalities in newborn infants have been reported. Diagnosing ZIKV infection remains a challenge, as viral RNA detection is only applicable until a few days after the onset of symptoms. After that, serological tests must be applied, and, as expected, high cross-reactivity between ZIKV and other flavivirus serology is observed. Plaque reduction neutralization test (PRNT) is indicated to confirm positive samples for being more specific, however it is laborious intensive and time consuming, representing a major bottleneck for patient diagnosis. To overcome this limitation, we developed a high-throughput image-based fluorescent neutralization test for ZIKV infection by serological detection. Using 226 human specimens, we showed that the new test presented higher throughput than traditional PRNT, maintaining the correlation between results. Furthermore, when tested with dengue virus samples, it showed 50.53% less cross reactivity than MAC-ELISA. This fluorescent neutralization test could be used for clinical diagnosis confirmation of ZIKV infection, as well as for vaccine clinical trials and seroprevalence studies.