Department of Tropical Medicine, Medical Microbiology and Pharmacology, John A. Burns School of Medicine, University of Hawaii at Manoa, Honolulu, HI, United States.
National Reference Laboratory for Dengue and Other Arboviruses, Virology Department, Research Institute for Tropical Medicine, Muntinlupa, Philippines.
Front Immunol. 2023 Jul 24;14:1202055. doi: 10.3389/fimmu.2023.1202055. eCollection 2023.
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.
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.
The 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.
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.
登革热病毒（DENV）是人类中由蚊子传播的病毒性疾病的主要原因。登革热疫苗（Dengvaxia）是首个获得许可的登革热疫苗，推荐用于 9-45 岁的 DENV 血清阳性个体。在菲律宾，2016-2017 年期间，在没有进行血清学检测的情况下，为 83 万多名儿童接种了 Dengvaxia。随后，研究表明，接受 Dengvaxia 接种的 DENV 血清阴性儿童在突破性 DENV 感染后会发展为严重疾病。因此，参加大规模疫苗接种运动的数千名儿童面临更高的重症登革热风险。开发和验证一种能够识别基线 DENV 无经验 Dengvaxia 受种者的检测方法至关重要。这将允许更频繁和广泛的评估，并及时治疗突破性 DENV 感染。
我们评估了夏威夷大学（UH）开发的候选检测方法（DENV1-4 非结构蛋白 1（NS1）IgG 酶联免疫吸附试验（ELISA））的性能，该检测方法使用了有充分记录的血清/血浆样本，包括 DENV 感染后 20 年以上的样本，并测试了来自 199 名研究参与者的样本，包括来自菲律宾发热监测计划的 100 名 Dengvaxia 受种者。
该检测方法的灵敏度和特异性分别为 96.6%和 99.4%，均高于疫苗接种前的筛查结果。在接种 Dengvaxia 时，DENV 无经验（10/23）的儿童发生症状性突破性 DENV 感染的比率明显高于 DENV 免疫（7/53）的儿童（p=0.004，Fisher 精确检验），表明该检测方法和算法在临床实践中的可行性。
UH DENV1-4 NS1 IgG ELISA 不仅可以在非急性登革热期间，而且可以在突破性 DENV 感染期间确定 Dengvaxia 受种者的基线 DENV 血清状态，这对评估 Dengvaxia 在上市后的长期安全性和有效性具有重要意义。
