AUTHOR=Dai Yu-Ching , Sy Ava Kristy , Jiz Mario , Tsai Jih-Jin , Bato Joan , Quinoñes Mary Ann , Reyes Mary Anne Joy , Wang Wei-Kung 

TITLE=Identification of prior dengue-naïve Dengvaxia recipients with an increased risk for symptomatic dengue during fever surveillance in the Philippines

JOURNAL=Frontiers in Immunology

VOLUME=Volume 14 - 2023

YEAR=2023

URL=https://www.frontiersin.org/journals/immunology/articles/10.3389/fimmu.2023.1202055

DOI=10.3389/fimmu.2023.1202055

ISSN=1664-3224

ABSTRACT=Introduction: Dengue 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. 
Methods: We 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. 
Results: The sensitivity and specificity of the assay was 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. 
Conclusion: The 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.