Although vaccination is considered the most effective method for preventing influenza, it shows limited efficacy in the elderly. Here, Nakaya et al used a systems vaccinology approach to understand the mechanisms behind poor vaccine efficacy in the inactivated influenza vaccine (TIV) in the elderly.
212 individuals from the current study and 218 individuals from a previously published study (Franco et al., 2013) were included in analyses. 54 of these were elderly (>65 years old). As expected, antibody responses to the Influenza vaccine (TIV) decrease with age.
Blood Transcriptomic Modules related to the induction of interferons and activation of dendritic cells were enriched on days 1 and 3 after TIV vaccination, whereas modules related to T cells at these time points were negatively associated with the antibody response. On day 7, there was a robust enrichment of antibody secreting cells (ASC) and cell cycle-related modules. The enriched modules in young and elderly were similar, particularly those related to the interferon response and activation of dendritic cells on day 1. However, the magnitude of expression of interferon-related genes was significantly higher in young individuals (See top figure).
Combining all datasets, several B-cell- and T-cell-related modules at pre-vaccination was positively correlated with an increased antibody response to vaccination. In contrast, modules related to monocytes were negatively correlated with antibody responses, supporting the concept that inflammatory responses at baseline might be detrimental to the induction of vaccine-induced antibody responses.
Consistent with the neutralizing antibody responses, B-cell and plasmablast modules (BTM S3) showed reduced expression in the elderly compared to the young on day 7. However, Natural killer (NK) cell and monocyte modules were enriched in the elderly at day 3 and day 7 after vaccination.
To examine if the transcriptional changes were due to changes in these specific cell types, flow cytometry was performed. Proportions of total NK cells in elderly subjects were higher than those of young subjects at baseline and all time points studied (days 0–14). The NK-cell activation markers were also more prominent in the elderly. Similarly, increased quantities of monocytes were seen in the elderly, with higher CCR5 expression at all time-points tested.
Differential expression of miRNA is also evident between the elderly and young, which suggests that miRNA could be important regulators of the immune response to influenza vaccination.
Data is deposited in GEO as GSE74817.