AS03-Adjuvanted H5N1 Avian Influenza Vaccine Modulates Early Innate Immune Signatures in Human Peripheral Blood Mononuclear Cells. (19th December 2018)

• Record Type: Journal Article
• Authors: Howard, Leigh M; Goll, Johannes B; Jensen, Travis L; Hoek, Kristen L; Prasad, Nripesh; Gelber, Casey E; Levy, Shawn E; Joyce, Sebastian; Link, Andrew J; Creech, C Buddy; Edwards, Kathryn M
• Is Part Of: Journal of infectious diseases. Volume 219:Number 11(2019)
• Page Start: 1786
• Page End: 1798
• Publication Date: 2018-12-19
• Subjects: adjuvant -- AS03 -- avian influenza -- influenza vaccine -- systems vaccinology; Communicable diseases -- Periodicals; Diseases -- Causes and theories of causation -- Periodicals; Medicine -- Periodicals; Communicable Diseases -- Periodicals; Electronic journals; 616.9
• DOI: 10.1093/infdis/jiy721
• Languages: English
• ISSNs: 0022-1899

Abstract

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. Abstract : Transcriptomic analysis of PBMCs after AS03-adjuvanted H5N1 vaccination revealed activation of several innate immune signaling pathways and strong upregulation of Fcγ-receptor genes. Although PBMCs and individual immune cell types shared key innate signals, unique signals were identified by both approaches.