Background:
Adjuvant System 03 (AS03) markedly enhances responses to influenza A/H5N1 vaccines, but the mechanisms of this enhancement are incompletely understood.
Methods:
Using RNA-Seq on peripheral blood mononuclear cells (PBMC) from AS03-adjuvanted and unadjuvanted inactivated H5N1 vaccine recipients, we identified differentially-expressed genes, enriched pathways, and genes that correlated with serologic responses. We compared bulk PBMC findings with our previously published assessments of flow-sorted immune cell types.
Results:
AS03-adjuvanted vaccine induced the strongest differential signals day 1 post-vaccination, activating multiple innate immune pathways including interferon and JAK-STAT signaling, FcγR-mediated phagocytosis, and antigen processing/presentation. Changes in signal transduction and immunoglobulin genes predicted peak hemagglutinin inhibition (HAI) titers. Compared to individual immune cell types, activated PBMC genes and pathways were most similar to innate immune cells. However, several pathways were unique to PBMC, and several pathways identified in individual cell types were absent in PBMC.
Conclusions:
Transcriptomic analysis of PBMC after AS03-adjuvanted H5N1 vaccination revealed early activation of innate immune signaling, including a 5-8-fold up-regulation of FcγR1A/1B/1C genes. Several early gene responses were correlated with HAI titer, indicating links with the adaptive immune response. While PBMC and cell-specific results shared key innate immune signals, unique signals were identified by both approaches.