Identification of prior dengue-naïve Dengvaxia recipients with an increased risk for symptomatic dengue during fever surveillance in the Philippines
IntroductionDengue virus (DENV) is the leading cause of mosquito-borne viral diseases in humans. Dengvaxia, the first licensed dengue vaccine, is recommended for DENV-seropositive individuals aged 9–45 years. In the Philippines, Dengvaxia was administered to more than 830,000 children without prior...
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Frontiers Media S.A.
2023-07-01
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Online Access: | https://www.frontiersin.org/articles/10.3389/fimmu.2023.1202055/full |
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author | Yu-Ching Dai Ava Kristy Sy Mario Jiz Jih-Jin Tsai Jih-Jin Tsai Jih-Jin Tsai Joan Bato Mary Ann Quinoñes Mary Anne Joy Reyes Wei-Kung Wang |
author_facet | Yu-Ching Dai Ava Kristy Sy Mario Jiz Jih-Jin Tsai Jih-Jin Tsai Jih-Jin Tsai Joan Bato Mary Ann Quinoñes Mary Anne Joy Reyes Wei-Kung Wang |
author_sort | Yu-Ching Dai |
collection | DOAJ |
description | IntroductionDengue virus (DENV) is the leading cause of mosquito-borne viral diseases in humans. Dengvaxia, the first licensed dengue vaccine, is recommended for DENV-seropositive individuals aged 9–45 years. In the Philippines, Dengvaxia was administered to more than 830,000 children without prior serological testing in 2016–2017. Subsequently, it was revealed that DENV-seronegative children who received Dengvaxia developed severe disease following breakthrough DENV infection. As a result, thousands of children participating in the mass vaccination campaign were at higher risk of severe dengue disease. It is vital that an assay that identifies baseline DENV-naïve Dengvaxia recipients be developed and validated. This would permit more frequent and extensive assessments and timely treatment of breakthrough DENV infections.MethodsWe evaluated the performance of a candidate assay, the DENV1–4 nonstructural protein 1 (NS1) IgG enzyme-linked immunosorbent assay (ELISA), developed by the University of Hawaii (UH), using well-documented serum/plasma samples including those >20 years post-DENV infection, and tested samples from 199 study participants including 100 Dengvaxia recipients from the fever surveillance programs in the Philippines.ResultsThe sensitivity and specificity of the assay were 96.6% and 99.4%, respectively, which are higher than those reported for pre-vaccination screening. A significantly higher rate of symptomatic breakthrough DENV infection was found among children that were DENV-naïve (10/23) than among those that were DENV-immune (7/53) when vaccinated with Dengvaxia (p=0.004, Fisher’s exact test), demonstrating the feasibility of the assay and algorithms in clinical practice.ConclusionThe UH DENV1–4 NS1 IgG ELISA can determine baseline DENV serostatus among Dengvaxia recipients not only during non-acute dengue but also during breakthrough DENV infection, and has implications for assessing the long-term safety and effectiveness of Dengvaxia in the post-licensure period. |
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spelling | doaj.art-968aa28b3cba4974ba00946a1e52bf962023-07-24T11:59:47ZengFrontiers Media S.A.Frontiers in Immunology1664-32242023-07-011410.3389/fimmu.2023.12020551202055Identification of prior dengue-naïve Dengvaxia recipients with an increased risk for symptomatic dengue during fever surveillance in the PhilippinesYu-Ching Dai0Ava Kristy Sy1Mario Jiz2Jih-Jin Tsai3Jih-Jin Tsai4Jih-Jin Tsai5Joan Bato6Mary Ann Quinoñes7Mary Anne Joy Reyes8Wei-Kung Wang9Department of Tropical Medicine, Medical Microbiology and Pharmacology, John A. Burns School of Medicine, University of Hawaii at Manoa, Honolulu, HI, United StatesNational Reference Laboratory for Dengue and Other Arboviruses, Virology Department, Research Institute for Tropical Medicine, Muntinlupa, PhilippinesImmunology Department, Research Institute for Tropical Medicine, Muntinlupa, PhilippinesTropical Medicine Center, Kaohsiung Medical University Hospital, Kaohsiung, TaiwanDivision of Infectious Diseases, Department of Internal Medicine, Kaohsiung Medical University Hospital, Kaohsiung, TaiwanSchool of Medicine, College of Medicine, Kaohsiung Medical University, Kaohsiung, TaiwanNational Reference Laboratory for Dengue and Other Arboviruses, Virology Department, Research Institute for Tropical Medicine, Muntinlupa, PhilippinesNational Reference Laboratory for Dengue and Other Arboviruses, Virology Department, Research Institute for Tropical Medicine, Muntinlupa, PhilippinesNational Reference Laboratory for Dengue and Other Arboviruses, Virology Department, Research Institute for Tropical Medicine, Muntinlupa, PhilippinesDepartment of Tropical Medicine, Medical Microbiology and Pharmacology, John A. Burns School of Medicine, University of Hawaii at Manoa, Honolulu, HI, United StatesIntroductionDengue virus (DENV) is the leading cause of mosquito-borne viral diseases in humans. Dengvaxia, the first licensed dengue vaccine, is recommended for DENV-seropositive individuals aged 9–45 years. In the Philippines, Dengvaxia was administered to more than 830,000 children without prior serological testing in 2016–2017. Subsequently, it was revealed that DENV-seronegative children who received Dengvaxia developed severe disease following breakthrough DENV infection. As a result, thousands of children participating in the mass vaccination campaign were at higher risk of severe dengue disease. It is vital that an assay that identifies baseline DENV-naïve Dengvaxia recipients be developed and validated. This would permit more frequent and extensive assessments and timely treatment of breakthrough DENV infections.MethodsWe evaluated the performance of a candidate assay, the DENV1–4 nonstructural protein 1 (NS1) IgG enzyme-linked immunosorbent assay (ELISA), developed by the University of Hawaii (UH), using well-documented serum/plasma samples including those >20 years post-DENV infection, and tested samples from 199 study participants including 100 Dengvaxia recipients from the fever surveillance programs in the Philippines.ResultsThe sensitivity and specificity of the assay were 96.6% and 99.4%, respectively, which are higher than those reported for pre-vaccination screening. A significantly higher rate of symptomatic breakthrough DENV infection was found among children that were DENV-naïve (10/23) than among those that were DENV-immune (7/53) when vaccinated with Dengvaxia (p=0.004, Fisher’s exact test), demonstrating the feasibility of the assay and algorithms in clinical practice.ConclusionThe UH DENV1–4 NS1 IgG ELISA can determine baseline DENV serostatus among Dengvaxia recipients not only during non-acute dengue but also during breakthrough DENV infection, and has implications for assessing the long-term safety and effectiveness of Dengvaxia in the post-licensure period.https://www.frontiersin.org/articles/10.3389/fimmu.2023.1202055/fulldengue virusvaccineDengvaxiaserostatusenzyme-linked immunosorbent assay |
spellingShingle | Yu-Ching Dai Ava Kristy Sy Mario Jiz Jih-Jin Tsai Jih-Jin Tsai Jih-Jin Tsai Joan Bato Mary Ann Quinoñes Mary Anne Joy Reyes Wei-Kung Wang Identification of prior dengue-naïve Dengvaxia recipients with an increased risk for symptomatic dengue during fever surveillance in the Philippines Frontiers in Immunology dengue virus vaccine Dengvaxia serostatus enzyme-linked immunosorbent assay |
title | Identification of prior dengue-naïve Dengvaxia recipients with an increased risk for symptomatic dengue during fever surveillance in the Philippines |
title_full | Identification of prior dengue-naïve Dengvaxia recipients with an increased risk for symptomatic dengue during fever surveillance in the Philippines |
title_fullStr | Identification of prior dengue-naïve Dengvaxia recipients with an increased risk for symptomatic dengue during fever surveillance in the Philippines |
title_full_unstemmed | Identification of prior dengue-naïve Dengvaxia recipients with an increased risk for symptomatic dengue during fever surveillance in the Philippines |
title_short | Identification of prior dengue-naïve Dengvaxia recipients with an increased risk for symptomatic dengue during fever surveillance in the Philippines |
title_sort | identification of prior dengue naive dengvaxia recipients with an increased risk for symptomatic dengue during fever surveillance in the philippines |
topic | dengue virus vaccine Dengvaxia serostatus enzyme-linked immunosorbent assay |
url | https://www.frontiersin.org/articles/10.3389/fimmu.2023.1202055/full |
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