Systematic name M40938
Brief description Genes down-regulated in peripheral blood mononuclear cell vaccinated with AS03 adjuvant vs phosphate-bufferred saline in adults (19-39) after exposure to inactivated monovalent influenza A/Indonesia/05/2005 H5N1 split-virus vaccine , time point 1D , administered i.m.
Full description or 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, Fcgamma receptor (FcgammaR)-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 Fc-gammaR1A/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.
Collection C7: Immunologic Signature
      VAX: HIPC Vaccine Response
Source publication Pubmed 30566602   Authors: Howard LM,Goll JB,Jensen TL,Hoek KL,Prasad N,Gelber CE,Levy SE,Joyce S,Link AJ,Creech CB,Edwards KM
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