Posted in influenza, Resource

Systems biology of immunity to MF59-adjuvanted versus nonadjuvanted trivalent seasonal influenza vaccines in early childhood

Figure showing that the differentially expressed genes (DEGs) were significantly higher in adults compared to children under 2 years of age. Overall, the adjuvanted inactivated influenza vaccine generated more DEGs than the unadjuvanted counterpart. Source from Nakaya et al., PNAS, 2016.

The trivalent inactivated influenza vaccine (TIV) is poorly immunogenic and has low effectiveness under 2 years of age. In this study by Nakaya et al., 2016 , the investigators studied the innate, adaptive and molecular responses to the seasonal TIV and MF59-adjuvanted TIV (ATIV) in 90 children from 14- to 24-months of age.

At day 28 post-boost, HAI geometric mean titers were higher in ATIV vaccinees compared with TIV. However, the magnitude of the plasmablast response was much lower in children than in adults. TIV and ATIV induced a similar magnitude of IgM- and IgG-secreting plasmablast cells in children.

MF59-adjuvanted TIV vaccine induced a higher expansion of multicytokine-producing vaccine-specific CD4+ T cells, mostly producing TNF-α and IL-2.

ATIV induced more alterations in gene expression at days 1, 3, and 7 post-boost compared with TIV. However, the numbers of DEGs were much smaller than in an adult cohort. There was high heterogeneity in the individual host responses, which could have accounted for the fewer DEGs detected.

Gene set enrichment analysis (GSEA) on individual subject’s responses revealed that at day 1 post vaccination, the positively enriched modules are M75 “antiviral interferon signature,” S5 “dendritic cell signature,” M16 “Toll-like receptor (TLR) and inflammatory signaling.” Among the negatively enriched modules, several modules related to T-cell function, NK cells, and cell cycle were found, including M7.1 “T cell activation,” M7.2 “enriched in NK cells,” and M4.0 “cell cycle and transcription”

GSEA was also applied to rank genes based on correlation with HAI titers. These modules include M75 “antiviral interferon signature,” M165 “enriched in activated dendritic cells,” and several others. These modules were positively correlated with HAI response at days 1, 7, and 28 following the booster shot.

The kinetics of enrichment of two blood transcriptomic modules associated with antibody-secreting cells (M156.1 and S3) show that enrichment is higher on days 7 and 28 for ATIV. The M156.1 module “plasma cell, immunoglobulins” was only significant at day 28 postboost, suggesting that unlike in adults, the expansion of antibody secreting cells may occur after day 7.

Overall, these findings highlight the differences in host immune responses between children and adults.

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