Prior upregulation of interferon pathways in the nasopharynx impacts viral shedding following live attenuated influenza vaccine challenge in children.
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Authors
Costa-Martins, André G
Lindsey, Benjamin B
Ogava, Rodrigo LT
Castro, Ícaro
Jagne, Ya Jankey
Sallah, Hadijatou J
Armitage, Edwin P
Jarju, Sheikh
Ahadzie, Bankole
Ellis-Watson, Rebecca
Tregoning, John S
Bingle, Colin D
Bogaert, Debby
Clarke, Ed
Ordovas-Montanes, Jose
Jeffries, David
Kampmann, Beate
Nakaya, Helder I
de Silva, Thushan I
Publication Date
2021-12-21Journal Title
Cell Rep Med
ISSN
2666-3791
Publisher
Elsevier BV
Volume
2
Issue
12
Number
ARTN 100465
Pages
100465
Type
Article
This Version
VoR
Physical Medium
Electronic-eCollection
Metadata
Show full item recordCitation
Costa-Martins, A. G., Mane, K., Lindsey, B. B., Ogava, R. L., Castro, Í., Jagne, Y. J., Sallah, H. J., et al. (2021). Prior upregulation of interferon pathways in the nasopharynx impacts viral shedding following live attenuated influenza vaccine challenge in children.. Cell Rep Med, 2 (12. ARTN 100465), 100465. https://doi.org/10.1016/j.xcrm.2021.100465
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.
Keywords
LAIV, asymptomatic respiratory viral infection, influenza, interferon-stimulated genes, mucosal, transcriptome
Identifiers
External DOI: https://doi.org/10.1016/j.xcrm.2021.100465
This record's URL: https://www.repository.cam.ac.uk/handle/1810/333626
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