Translational Sciences and Biomarkers, Sanofi Pasteur, Swiftwater, PA, USA; Global Clinical Sciences, Sanofi Pasteur, Swiftwater, PA, USA.
Global Clinical Immunology, Sanofi Pasteur, Swiftwater, PA, USA.
Lancet Microbe. 2022 Jun;3(6):e427-e434. doi: 10.1016/S2666-5247(22)00033-7. Epub 2022 May 4.
A dengue pre-vaccination test that is convenient, highly specific, and highly sensitive is still needed. The OnSite Dengue IgG rapid diagnostic test (RDT) is a new rapid diagnostic test specifically designed for pre-vaccination screening. We aimed to retrospectively assess the efficacy of a tetravalent dengue vaccine (CYD-TDV) in participants determined to be dengue seropositive by the OnSite IgG RDT and to evaluate assay performances.
This was a complementary study using pre-vaccination samples from two CYD-TDV efficacy trials done in five countries in the Asia-Pacific region (NCT01373281) and five countries in Latin America (NCT01374516). Baseline dengue serostatus was determined by the OnSite IgG RDT on samples from the immunogenicity subsets of the two trials. In participants who were test positive, we calculated CYD-TDV vaccine efficacy against symptomatic virologically confirmed dengue (VCD) over 25 months, and against hospitalisation with VCD over 72 months of follow-up after the first vaccination. We used a reference algorithm to determine the reference dengue serostatus for each sample, and sensitivity and specificity of the OnSite IgG RDT were calculated. Analyses were done on the whole population (aged 2-16 years), and on those aged 6 years or older and those aged 9 years or older.
Of 3983 participants in the immunogenicity subsets of the efficacy trials CYD14 and CYD15, 3962 had complete dengue reference test results enabling baseline serostatus classification and 3833 had sufficient serum samples remaining for evaluation with the OnSite IgG RDT. Of the samples tested, 2486 (64·9%) of 3833 were OnSite IgG RDT-positive. In participants aged 2-16 years who were OnSite IgG RDT-positive, vaccine efficacy was 84·1% (95% CI 71·6-91·1) against symptomatic VCD, and 69·2% (38·8-84·5) against hospitalisation with VCD, with similar findings in those aged 6 years or older and those aged 9 years or older. The OnSite IgG RDT showed very high sensitivity (91·1%, 89·9-92·1) and high specificity (92·8%, 91·2-94·2) in participants aged 2-16 years, with significantly higher specificity in those aged 9 years or older (96·6%, 94·9-97·8).
The OnSite IgG RDT should provide a valuable tool for screening for previous dengue infection at the point of vaccination. In individuals who were OnSite IgG RDT-positive, the vaccine efficacy of CYD-TDV was high across all three age groups.
Sanofi Pasteur.
我们仍需要一种方便、高度特异和敏感的登革热疫苗前检测方法。OnSite Dengue IgG 快速诊断检测（RDT）是一种专门为疫苗前筛查而设计的新的快速诊断检测方法。我们旨在回顾性评估一种四价登革热疫苗（CYD-TDV）在通过 OnSite IgG RDT 检测为登革热血清阳性的参与者中的疗效，并评估检测方法的性能。
这是一项使用来自亚太地区五个国家（NCT01373281）和拉丁美洲五个国家的两项 CYD-TDV 疗效试验的免疫亚组的疫苗前样本进行的补充研究（NCT01374516）。使用 OnSite IgG RDT 在两个试验的免疫亚组样本上确定基线登革热血清状态。在检测阳性的参与者中，我们计算了 CYD-TDV 疫苗对 25 个月内出现症状性病毒确诊登革热（VCD）的疗效，以及对首次接种后 72 个月内因 VCD 住院的疗效。我们使用参考算法确定了每个样本的参考登革热血清状态，并计算了 OnSite IgG RDT 的敏感性和特异性。分析在整个人群（2-16 岁）以及 6 岁或以上和 9 岁或以上的人群中进行。
在疗效试验 CYD14 和 CYD15 的免疫亚组中，共有 3983 名参与者，其中 3962 名有完整的登革热参考检测结果，可对血清状态进行分类，3833 名有足够的血清样本可用于 OnSite IgG RDT 评估。在检测的样本中，3833 个中有 2486 个（64.9%）为 OnSite IgG RDT 阳性。在 2-16 岁的 OnSite IgG RDT 阳性参与者中，疫苗对症状性 VCD 的疗效为 84.1%（95%CI 71.6-91.1），对因 VCD 住院的疗效为 69.2%（38.8-84.5），6 岁或以上和 9 岁或以上的参与者中也有类似发现。在 2-16 岁的参与者中，OnSite IgG RDT 具有非常高的敏感性（91.1%，89.9-92.1）和高特异性（92.8%，91.2-94.2），9 岁或以上的参与者的特异性显著更高（96.6%，94.9-97.8）。
OnSite IgG RDT 应该是在疫苗接种点筛查既往登革热感染的一个有价值的工具。在 OnSite IgG RDT 阳性的个体中，CYD-TDV 的疫苗效力在所有三个年龄组中均较高。
赛诺菲巴斯德。
