Systematic name M40996
Brief description Genes up-regulated in neutrophil 1d vs 0d in adults (18-49) 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: 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: 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_neu_d1
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Organism Homo sapiens
Source platform HUMAN_GENE_SYMBOL
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Version history 7.3: First Introduced.

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