Serotype-specific detection of dengue viruses in a nonstructural protein 1-based enzyme-linked immunosorbent assay validated with a multinational cohort

Authors

Bosch, Irene; Reddy, Ankita; de Puig, Helena; Ludert, Juan E.; Perdomo-Celis, Federico; Narváez, Calos F.; Versiani, Alice; Fandos, Diana; Nogueira, Mauricio L.; Singla, Mohit; Lodha, Rakesh; Medigeshi, Guruprasad R.; Lorenzana, Ivette; Ralde, Hugo Vicente; Gelvez-Ramirez, Margarita; Villar, Luis A.; Hiley, Megan; Mendoza, Laura; Salcedo, Nol; Herrera, Bobby Brooke; Gehrke, Lee

Abstract

Dengue virus (DENV) infection is an increasingly significant threat to global health, with a yearly estimate of 390 million infections and an expected increasing burden with the rise of climate change and globalization. DENV is caused by one of the four serotypes (DENV-1-4), each of which have been associated with different immune responses and clinical manifestations. We developed a method to detect DENV serotypes by targeting the nonstructural 1 (NS1) antigen through an enzyme-linked immunosorbent-based assay (ELISA) with high sensitivity and specificity. We demonstrate that our high throughput mouse-derived antibody screening method selected for optimal test performance. The antibodies were integrated into an ELISA that can distinguish between the four different dengue serotypes by serotype-specific pairing. In addition, we provide a dengue universal antibody combination that enables pan-virus detection independently of the serotype. We use the ELISA in three different countries and calculate overall and site-specific sensitivities and specificities. The assay performs optimally when levels of viremia are high during the first five days of fever.