Human Gene Set: HOWARD_DENDRITIC_CELL_INACT_MONOV
_INFLUENZA_A_INDONESIA_05_2005_H5N1_AGE
_18_49YO_3DY_UP

Standard name

HOWARD_DENDRITIC_CELL_INACT_MONOV_INFLUENZA_A_INDONESIA_05_2005_H5N1_AGE_18_49YO_3DY_UP

Systematic name

M40947

Brief description

Genes up-regulated in dendritic cell 3d vs 0d in adults (18-49) after exposure to inactivated monovalent influenza A/Indonesia/05/2005 H5N1 split-virus vaccine , time point 3D , administered i.m.

Full description or abstract

BACKGROUND: Vaccine development for influenza A/H5N1 is an important public health priority, but H5N1 vaccines are less immunogenic than seasonal influenza vaccines. Adjuvant System 03 (AS03) markedly enhances immune responses to H5N1 vaccine antigens, but the underlying molecular mechanisms are incompletely understood. OBJECTIVE: We compared the safety (primary endpoint), immunogenicity (secondary), gene expression (tertiary) and cytokine responses (exploratory) between AS03-adjuvanted and unadjuvanted inactivated split-virus H5N1 influenza vaccines. In a double-blinded clinical trial, we randomized twenty adults aged 18-49 to receive two doses of either AS03-adjuvanted (n = 10) or unadjuvanted (n = 10) H5N1 vaccine 28 days apart. We used a systems biology approach to characterize and correlate changes in serum cytokines, antibody titers, and gene expression levels in six immune cell types at 1, 3, 7, and 28 days after the first vaccination. RESULTS: Both vaccines were well-tolerated. Nine of 10 subjects in the adjuvanted group and 0/10 in the unadjuvanted group exhibited seroprotection (hemagglutination inhibition antibody titer > 1:40) at day 56. Within 24 hours of AS03-adjuvanted vaccination, increased serum levels of IL-6 and IP-10 were noted. Interferon signaling and antigen processing and presentation-related gene responses were induced in dendritic cells, monocytes, and neutrophils. Upregulation of MHC class II antigen presentation-related genes was seen in neutrophils. Three days after AS03-adjuvanted vaccine, upregulation of genes involved in cell cycle and division was detected in NK cells and correlated with serum levels of IP-10. Early upregulation of interferon signaling-related genes was also found to predict seroprotection 56 days after first vaccination. CONCLUSIONS: Using this cell-based systems approach, novel mechanisms of action for AS03-adjuvanted pandemic influenza vaccination were observed. TRIAL: ClinicalTrials.gov NCT01573312.

Collection

C7: Immunologic Signature
VAX: HIPC Vaccine Response

Source publication

Pubmed 28099485 Authors: Howard LM,Hoek KL,Goll JB,Samir P,Galassie A,Allos TM,Niu X,Gordy LE,Creech CB,Prasad N,Jensen TL,Hill H,Levy SE,Joyce S,Link AJ,Edwards KM

Exact source

s4_dnc_d3

Related gene sets