AI Article Synopsis
- The AS03 adjuvant significantly boosts immune responses to the H5N1 influenza vaccine, though the exact mechanisms are not fully understood.
- Using RNA sequencing on immune cells from vaccinated individuals, researchers discovered that AS03 activates key immune pathways soon after vaccination, particularly in innate immune cells.
- The study found specific gene expressions correlated with vaccine efficacy, suggesting a strong link between early immune signaling and the eventual adaptive immune response.
Article Abstract
Background: Adjuvant System 03 (AS03) markedly enhances responses to influenza A/H5N1 vaccines, but the mechanisms of this enhancement are incompletely understood.
Methods: Using ribonucleic acid sequencing on peripheral blood mononuclear cells (PBMCs) 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 on day 1 postvaccination, activating multiple innate immune pathways including interferon and JAK-STAT signaling, Fcγ receptor (FcγR)-mediated phagocytosis, and antigen processing and presentation. Changes in signal transduction and immunoglobulin genes predicted peak hemagglutinin inhibition (HAI) titers. Compared with individual immune cell types, activated PBMC genes and pathways were most similar to innate immune cells. However, several pathways were unique to PBMCs, and several pathways identified in individual cell types were absent in PBMCs.
Conclusions: Transcriptomic analysis of PBMCs after AS03-adjuvanted H5N1 vaccination revealed early activation of innate immune signaling, including a 5- to 8-fold upregulation of FcγR1A/1B/1C genes. Several early gene responses were correlated with HAI titer, indicating links with the adaptive immune response. Although PBMCs and cell-specific results shared key innate immune signals, unique signals were identified by both approaches.
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| http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6500554 | PMC |
| http://dx.doi.org/10.1093/infdis/jiy721 | DOI Listing |
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