Serotype-specific detection of dengue viruses in a nonstructural protein 1-based enzyme-linked immunosorbent assay validated with a multi-national cohort.
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 challeng...
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ftdoajarticles:oai:doaj.org/article:5778c22a82e441fe87826d8102e1a0f3 2023-05-15T15:16:25+02:00 Serotype-specific detection of dengue viruses in a nonstructural protein 1-based enzyme-linked immunosorbent assay validated with a multi-national cohort. Irene Bosch Ankita Reddy Helena de Puig Juan E Ludert Federico Perdomo-Celis Carlos F Narváez Alice Versiani Diana Fandos Mauricio L Nogueira Mohit Singla Rakesh Lodha Guruprasad R Medigeshi Ivette Lorenzana Hugo Vicente Ralde Margarita Gélvez-Ramírez Luis A Villar Megan Hiley Laura Mendoza Nol Salcedo Bobby Brooke Herrera Lee Gehrke 2020-06-01T00:00:00Z https://doi.org/10.1371/journal.pntd.0008203 https://doaj.org/article/5778c22a82e441fe87826d8102e1a0f3 EN eng Public Library of Science (PLoS) https://doi.org/10.1371/journal.pntd.0008203 https://doaj.org/toc/1935-2727 https://doaj.org/toc/1935-2735 1935-2727 1935-2735 doi:10.1371/journal.pntd.0008203 https://doaj.org/article/5778c22a82e441fe87826d8102e1a0f3 PLoS Neglected Tropical Diseases, Vol 14, Iss 6, p e0008203 (2020) Arctic medicine. Tropical medicine RC955-962 Public aspects of medicine RA1-1270 article 2020 ftdoajarticles https://doi.org/10.1371/journal.pntd.0008203 2022-12-31T10:07:30Z 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 differentiating 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 sensitivity of the test for pan-DENV was 79.66% (325/408), and the sensitivities for DENV-1-4 serotyping 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. Article in Journal/Newspaper Arctic Human health Directory of Open Access Journals: DOAJ Articles Arctic PLOS Neglected Tropical Diseases 14 6 e0008203 |
institution |
Open Polar |
collection |
Directory of Open Access Journals: DOAJ Articles |
op_collection_id |
ftdoajarticles |
language |
English |
topic |
Arctic medicine. Tropical medicine RC955-962 Public aspects of medicine RA1-1270 |
spellingShingle |
Arctic medicine. Tropical medicine RC955-962 Public aspects of medicine RA1-1270 Irene Bosch Ankita Reddy Helena de Puig Juan E Ludert Federico Perdomo-Celis Carlos F Narváez Alice Versiani Diana Fandos Mauricio L Nogueira Mohit Singla Rakesh Lodha Guruprasad R Medigeshi Ivette Lorenzana Hugo Vicente Ralde Margarita Gélvez-Ramírez Luis A Villar Megan Hiley Laura Mendoza Nol Salcedo Bobby Brooke Herrera Lee Gehrke Serotype-specific detection of dengue viruses in a nonstructural protein 1-based enzyme-linked immunosorbent assay validated with a multi-national cohort. |
topic_facet |
Arctic medicine. Tropical medicine RC955-962 Public aspects of medicine RA1-1270 |
description |
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 differentiating 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 sensitivity of the test for pan-DENV was 79.66% (325/408), and the sensitivities for DENV-1-4 serotyping 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. |
format |
Article in Journal/Newspaper |
author |
Irene Bosch Ankita Reddy Helena de Puig Juan E Ludert Federico Perdomo-Celis Carlos F Narváez Alice Versiani Diana Fandos Mauricio L Nogueira Mohit Singla Rakesh Lodha Guruprasad R Medigeshi Ivette Lorenzana Hugo Vicente Ralde Margarita Gélvez-Ramírez Luis A Villar Megan Hiley Laura Mendoza Nol Salcedo Bobby Brooke Herrera Lee Gehrke |
author_facet |
Irene Bosch Ankita Reddy Helena de Puig Juan E Ludert Federico Perdomo-Celis Carlos F Narváez Alice Versiani Diana Fandos Mauricio L Nogueira Mohit Singla Rakesh Lodha Guruprasad R Medigeshi Ivette Lorenzana Hugo Vicente Ralde Margarita Gélvez-Ramírez Luis A Villar Megan Hiley Laura Mendoza Nol Salcedo Bobby Brooke Herrera Lee Gehrke |
author_sort |
Irene Bosch |
title |
Serotype-specific detection of dengue viruses in a nonstructural protein 1-based enzyme-linked immunosorbent assay validated with a multi-national cohort. |
title_short |
Serotype-specific detection of dengue viruses in a nonstructural protein 1-based enzyme-linked immunosorbent assay validated with a multi-national cohort. |
title_full |
Serotype-specific detection of dengue viruses in a nonstructural protein 1-based enzyme-linked immunosorbent assay validated with a multi-national cohort. |
title_fullStr |
Serotype-specific detection of dengue viruses in a nonstructural protein 1-based enzyme-linked immunosorbent assay validated with a multi-national cohort. |
title_full_unstemmed |
Serotype-specific detection of dengue viruses in a nonstructural protein 1-based enzyme-linked immunosorbent assay validated with a multi-national cohort. |
title_sort |
serotype-specific detection of dengue viruses in a nonstructural protein 1-based enzyme-linked immunosorbent assay validated with a multi-national cohort. |
publisher |
Public Library of Science (PLoS) |
publishDate |
2020 |
url |
https://doi.org/10.1371/journal.pntd.0008203 https://doaj.org/article/5778c22a82e441fe87826d8102e1a0f3 |
geographic |
Arctic |
geographic_facet |
Arctic |
genre |
Arctic Human health |
genre_facet |
Arctic Human health |
op_source |
PLoS Neglected Tropical Diseases, Vol 14, Iss 6, p e0008203 (2020) |
op_relation |
https://doi.org/10.1371/journal.pntd.0008203 https://doaj.org/toc/1935-2727 https://doaj.org/toc/1935-2735 1935-2727 1935-2735 doi:10.1371/journal.pntd.0008203 https://doaj.org/article/5778c22a82e441fe87826d8102e1a0f3 |
op_doi |
https://doi.org/10.1371/journal.pntd.0008203 |
container_title |
PLOS Neglected Tropical Diseases |
container_volume |
14 |
container_issue |
6 |
container_start_page |
e0008203 |
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1766346712559910912 |