Prior upregulation of interferon pathways in the nasopharynx impacts viral shedding following live attenuated influenza vaccine challenge in children
File(s)
Published version
Author(s)
Type
Journal Article
Abstract
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.
Date Issued
2021-12
Date Acceptance
2021-11-12
Citation
Cell Reports Medicine, 2021, 2 (12), pp.1-16
ISSN
2666-3791
Publisher
Elsevier BV
Start Page
1
End Page
16
Journal / Book Title
Cell Reports Medicine
Volume
2
Issue
12
Copyright Statement
© 2021 The Author(s). This is an open access article under the CC BY license (http://creativecommons.org/licenses/by/4.0/).
License URL
Sponsor
Medical Research Council (MRC)
Medical Research Council (MRC)
Identifier
https://www.sciencedirect.com/science/article/pii/S2666379121003372?via%3Dihub
Grant Number
MR/R005982/1
MR/R005982/1
Subjects
Science & Technology
Life Sciences & Biomedicine
Cell Biology
Medicine, Research & Experimental
Research & Experimental Medicine
SEASONAL INFLUENZA
VIRUS
Publication Status
Published
Article Number
100465
Date Publish Online
2021-12-09