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Serotype-specific detection of dengue viruses in a nonstructural protein 1-based enzyme-linked immunosorbent assay validated with a multi-national cohort
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file.pdf
Description
Published version
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1.16 MB
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Adobe PDF
Checksum (MD5)
c8b97368d7dedb30bcbec35dc4f90c8d
Author(s)
Bosch, Irene
Reddy, Ankita
de Puig, Helena
Ludert, Juan E
Perdomo-Celis, Federico
Narváez, Carlos F
Versiani, Alice
Fandos, Diana
Nogueira, Mauricio L
Singla, Mohit
Date Issued
2020
Journal
PLoS Neglected Tropical Diseases
Publisher
Public Library of Science (PLoS)
Citation
Bosch, Irene, Reddy, Ankita, de Puig, Helena, Ludert, Juan E, Perdomo-Celis, Federico et al. 2020. "Serotype-specific detection of dengue viruses in a nonstructural protein 1-based enzyme-linked immunosorbent assay validated with a multi-national cohort." PLoS Neglected Tropical Diseases, 14 (6).
Version
Final published version
Abstract
© 2020 Bosch et al. Background Dengue virus (DENV) infections pose one of the largest global barriers to human health. The four serotypes (DENV 1–4) present different symptoms and influence immune response to subsequent DENV infections, rendering surveillance, risk assessments, and disease control particularly challenging. Early diagnosis and appropriate clinical management is critical and can be achieved by detecting DENV nonstructural protein 1 (NS1) in serum during the acute phase. However, few NS1-based tests have been developed that are capable of differentiat-ing DENV serotypes and none are currently commercially available. Methodology/Principle findings We developed an enzyme-linked immunosorbent assay (ELISA) to distinguish DENV-1-4 NS1 using serotype-specific pairs of monoclonal antibodies. A total of 1,046 antibodies were harvested from DENV-immunized mice and screened for antigen binding affinity. ELISA clinical performance was evaluated using 408 polymerase chain reaction-confirmed dengue samples obtained from patients in Brazil, Honduras, and India. The overall sensitiv-ity of the test for pan-DENV was 79.66% (325/408), and the sensitivities for DENV-1-4 sero-typing were 79.1% (38/48), 80.41% (78/97), 100% (45/45), and 79.6% (98/123), respectively. Specificity reached 94.07–100%. Significance Our study demonstrates a robust antibody screening strategy that enabled the development of a serotype NS1-based ELISA with maximized specific and sensitive antigen binding. This sensitive and specific assay also utilized the most expansive cohort to date, and of which about half are from Latin America, a geographic region severely underrepresented in previous similar studies. This ELISA test offers potential enhanced diagnostics during the acute phase of infection to help guide patient care and disease control. These results indicate that this ELISA is a promising aid in early DENV-1-4 diagnosis and surveillance in regions of endemicity in addition to offer convenient monitoring for future vaccine interventions.
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Creative Commons Attribution 4.0 International license
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DOI of Published Version
10.1371/JOURNAL.PNTD.0008203
