Prior upregulation of interferon pathways in the nasopharynx impacts viral shedding following live attenuated influenza vaccine challenge in children

Summary 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.
Graphical abstract
Highlights • 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.