Multi-parameter approach to evaluate the timing of memory status after 17DD-YF primary vaccination
Multi-parameter approach to evaluate the timing of memory status after 17DD-YF primary vaccination
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DOI：
10.1371/journal.pntd.0006462
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发表时间：
2018-06-01
影响因子：
3.8
通讯作者：
Martins-Filho, Olindo Assis
中科院分区：
文献类型：
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作者：
Costa-Pereira, Christiane;Campi-Azevedo, Ana Carolina;Martins-Filho, Olindo Assis
在这项研究中，应用机器增强技术带来科学见解，以确定疫苗接种后黄热病(YF)疫苗接种后跟进的表型/功能记忆相关生物标记物的最小集合。为此目的，监测循环T细胞(Naive/early-effector/Central-Memory/Effector-Memory)和B细胞(幼稚/非经典记忆/经典记忆)的记忆状态以及细胞因子谱(干扰素/肿瘤坏死因子/白介素5/白介素10)在接种NV前(第0天)和接种17DD-YF后的不同时间点-PV(第30-45天)、PV(第1-9年)和PV(第10-11年)。在PV(第30-45天)中观察到一组生物标志物(eEfCD_4；EMCD_4；CMCD_19；EMCD_8；IFNCD_4；IL-5CD8；TNFCD_4；IL-5CD19；IL-5CD_4)，而在NV(第0天)中未观察到，其中大部分仍在PV(1~9天)中观察到。在NV(第0天)观察到表型/功能生物标记物的缺陷，而在PV(10-11岁)观察到完全缺乏与记忆相关的属性，与初次接种时的年龄无关。文氏图分析预先选取了10个属性(eEfCD_4、EMCD_4、CMCD_19、EMCD_8、IFNCD_4、IL-5CD8、TNFCD_4、IFN_CD8、TNFCD8和IL-5CD_4)，其中总平均值对区分PV(第30-45天)和PV(第1-9年)和NV(第0天)和PV(第10-11年)具有中等的准确性。多参数方法和决策树算法将EMCD8和IL-5CD4属性定义为性能适中的前两个预测因子。与PRNT滴度一起，前两个生物标志物导致了在PV(第30-45天)和PV(1-9岁)志愿者中观察到的80%和51%的结果记忆状态，相比之下，在NV(0天)和PV(10-11岁)中分别有0%和29%的人观察到记忆状态。在PV(10-11年)观察到的记忆相关属性的不足突出表明，在17DD-YF初级疫苗接种后，结果记忆明显随时间减少，这可能有助于监测YF传播风险地区的潜在保护相关性。
In this investigation, machine-enhanced techniques were applied to bring about scientific insights to identify a minimum set of phenotypic/functional memory-related biomarkers for post-vaccination follow-up upon yellow fever (YF) vaccination. For this purpose, memory status of circulating T-cells (Naive/early-effector/Central-Memory/Effector-Memory) and B-cells (Naive/non-Classical-Memory/Classical-Memory) along with the cytokine profile (IFN/TNF/IL-5/IL-10) were monitored before-NV(day0) and at distinct time-points after 17DD-YF primary vaccination-PV(day30-45); PV(year1-9) and PV(year10-11). A set of biomarkers (eEfCD4; EMCD4; CMCD19; EMCD8; IFNCD4; IL-5CD8; TNFCD4; IFNCD8; TNFCD8; IL-5CD19; IL-5CD4) were observed in PV(day30-45), but not in NV(day0), with most of them still observed in PV(year1-9). Deficiencies of phenotypic/functional biomarkers were observed in NV(day0), while total lack of memory-related attributes was observed in PV (year10-11), regardless of the age at primary vaccination. Venn-diagram analysis preselected 10 attributes (eEfCD4, EMCD4, CMCD19, EMCD8, IFNCD4, IL-5CD8, TNFCD4, IFNCD8, TNFCD8 and IL-5CD4), of which the overall mean presented moderate accuracy to discriminate PV(day30-45)& PV(year1-9) from NV(day0)& PV(year10-11). Multi-parameter approaches and decision-tree algorithms defined the EMCD8 and IL-5CD4 attributes as the top-two predictors with moderated performance. Together with the PRNT titers, the top-two biomarkers led to a resultant memory status observed in 80% and 51% of volunteers in PV(day30-45) and PV(year1-9), contrasting with 0% and 29% found in NV(day0) and PV (year10-11), respectively. The deficiency of memory-related attributes observed at PV (year10-11) underscores the conspicuous time-dependent decrease of resultant memory following17DD-YF primary vaccination that could be useful to monitor potential correlates of protection in areas under risk of YF transmission.