Prior upregulation of interferon pathways in the nasopharynx impacts viral shedding following live attenuated influenza vaccine challenge in children.
Prior upregulation of interferon pathways in the nasopharynx impacts viral shedding following live attenuated influenza vaccine challenge in children.
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DOI：
10.1016/j.xcrm.2021.100465
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发表时间：
2021-12-21
期刊：
影响因子：
--
通讯作者：
de Silva TI
中科院分区：
文献类型：
--
作者：
Costa-Martins AG;Mane K;Lindsey BB;Ogava RLT;Castro Í;Jagne YJ;Sallah HJ;Armitage EP;Jarju S;Ahadzie B;Ellis-Watson R;Tregoning JS;Bingle CD;Bogaert D;Clarke E;Ordovas-Montanes J;Jeffries D;Kampmann B;Nakaya HI;de Silva TI
在缺乏流感特异性适应性免疫的儿童中，上呼吸道先天免疫反应可能会影响病毒复制和疾病结果。我们使用三价减毒流感活疫苗 (LAIV) 作为 24-59 个月儿童的替代攻击模型，以确定与随后病毒脱落相关的感染前粘膜转录组特征。 LAIV 之前干扰素信号通路的上调与第 2 天和第 7 天较低的毒株特异性病毒载量 (VL) 显着相关。一些干扰素刺激的基因在 LAIV 之前无症状呼吸道病毒感染的儿童中存在差异表达，并且与 LAIV VL 呈负相关。富含巨噬细胞、中性粒细胞和嗜酸性粒细胞的基因上调与较低的 VL 相关，并且在无症状病毒感染的儿童中更常见。儿童感染前粘膜干扰素基因表达的变异可能会影响随后的流感感染过程。这种变异性可能是由于频繁的呼吸道病毒感染造成的，这表明粘膜病毒与病毒相互作用在儿童中的潜在重要性。接种疫苗前上调粘膜干扰素可减少 LAIV 脱落 42% 的儿童出现无症状呼吸道病毒感染 其他呼吸道病毒感染导致干扰素基因表达升高 Costa-Martins 等人。研究表明，在流感疫苗株血清阴性的儿童中，在接受 LAIV 之前鼻咽干扰素基因上调与疫苗株脱落减少相关。无症状呼吸道病毒感染很常见，并导致干扰素基因表达升高，凸显了上呼吸道中病毒与病毒相互作用的重要性。
In children lacking influenza-specific adaptive immunity, upper respiratory tract innate immune responses may influence viral replication and disease outcome. We use trivalent live attenuated influenza vaccine (LAIV) as a surrogate challenge model in children aged 24–59 months to identify pre-infection mucosal transcriptomic signatures associated with subsequent viral shedding. Upregulation of interferon signaling pathways prior to LAIV is significantly associated with lower strain-specific viral loads (VLs) at days 2 and 7. Several interferon-stimulated genes are differentially expressed in children with pre-LAIV asymptomatic respiratory viral infections and negatively correlated with LAIV VLs. Upregulation of genes enriched in macrophages, neutrophils, and eosinophils is associated with lower VLs and found more commonly in children with asymptomatic viral infections. Variability in pre-infection mucosal interferon gene expression in children may impact the course of subsequent influenza infections. This variability may be due to frequent respiratory viral infections, demonstrating the potential importance of mucosal virus-virus interactions in children. Upregulated mucosal interferon prior to vaccination leads to reduced LAIV shedding Asymptomatic respiratory viral infections were seen in 42% of children Other respiratory viral infections contribute to higher interferon gene expression Costa-Martins et al. show that in children seronegative to influenza vaccine strains, upregulated nasopharyngeal interferon genes prior to LAIV receipt associates with reduced vaccine strain shedding. Asymptomatic respiratory viral infections are common and result in higher interferon gene expression, highlighting the importance of virus-virus interactions in the upper respiratory tract.
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