Vittrup Dorthe Maria, Jensen Andreas, Malon Michelle, Zimakoff Anne Cathrine, Kiehn Sørensen Jesper, Littell Brickley, Simões Eric A F, Svensson Jannet, Graff Stensballe Lone
Blegdamsvej 9, 2100 Copenhagen E, Denmark.
The National Danish University Hospital, Rigshospitalet, The Juliane Marie Center, Pediatric Department, Denmark.
Vaccine X. 2024 Aug 16;20:100548. doi: 10.1016/j.jvacx.2024.100548. eCollection 2024 Oct.
Assessing the risk of measles outbreaks and identifying the susceptible parts of the population is essential to timely intervention. Infants between 6-12 months are increasingly susceptible to measles but evaluating the performance of high throughput enzyme immunoassays (ELISAs) in infants < 9 months of age is lacking.
A commercially available ELISA kit (Creative Diagnostics, DEIA359) for estimating measles seroprotection was evaluated in infants 5-7 months of age. In an immunogenicity substudy in the Danish MMR trial conducted between 2019-2021, infants (and mothers at baseline) were sampled before and one month after measles-mumps-rubella vaccination (MMR) or placebo as well as one month after routine MMR at 15 months. Measles IgG ELISA was compared to the gold standard but labor-intensive measles plaque reduction neutralization test (PRNT) by Pearson and Spearman correlations and by estimating sensitivity, specificity, and positive and negative predictive values (PPV and NPV).
Measles IgG levels compared to PRNT antibodies had a Pearson's correlation coefficient between 0.10-0.24. Seroprotection rates measured by ELISA in young infants were 10-14% lower than measured by PRNT. The sensitivity of the ELISA to detect serological protection compared to PRNT in the infant population differed markedly across sampling time points and was 14%, 40%, and 92% at baseline, post-intervention, and post-routine MMR, whereas the specificity was 99%, 93%, and 43%, respectively. The PPV and NPV were 68% and 87% in infants at baseline.
The correlation between measles IgG and PRNT antibodies was low. Seroprotection was underestimated using ELISA. High-accuracy tests are needed to avoid misclassifications and practices that lead to primary or secondary vaccine failure or retention of vaccination in outbreak settings. Baseline PPV and NPV suggested some applicability of ELISA in predicting serological protection in this age group. However, PRNT may be the only accurate estimator of serological protection in young infants.
评估麻疹暴发风险并确定人群中的易感部分对于及时干预至关重要。6至12个月大的婴儿对麻疹的易感性日益增加，但缺乏对9个月以下婴儿中高通量酶免疫测定（ELISA）性能的评估。
在5至7个月大的婴儿中评估了一种用于估计麻疹血清保护的市售ELISA试剂盒（Creative Diagnostics，DEIA359）。在2019年至2021年进行的丹麦麻疹、腮腺炎和风疹疫苗（MMR）试验的免疫原性子研究中，婴儿（以及基线时的母亲）在麻疹、腮腺炎和风疹疫苗接种（MMR）或安慰剂之前和之后一个月以及15个月常规MMR之后一个月进行采样。通过Pearson和Spearman相关性以及估计敏感性、特异性以及阳性和阴性预测值（PPV和NPV），将麻疹IgG ELISA与金标准但劳动强度大的麻疹蚀斑减少中和试验（PRNT）进行比较。
与PRNT抗体相比，麻疹IgG水平的Pearson相关系数在0.10至0.24之间。ELISA测定的幼儿血清保护率比PRNT测定的低10%至14%。在婴儿群体中，与PRNT相比，ELISA检测血清学保护的敏感性在不同采样时间点差异显著，在基线、干预后和常规MMR后分别为14%、40%和92%，而特异性分别为99%、93%和43%。婴儿基线时的PPV和NPV分别为68%和87%。
麻疹IgG与PRNT抗体之间的相关性较低。使用ELISA低估了血清保护情况。需要高精度检测以避免导致原发性或继发性疫苗失败或在暴发环境中保留疫苗接种的错误分类和做法。基线PPV和NPV表明ELISA在预测该年龄组血清学保护方面有一定适用性。然而，PRNT可能是幼儿血清学保护的唯一准确估计方法。
