Gene expression signatures as a therapeutic target for severe H7N9 influenza – what do we know so far?

Systems biology approach: Panacea for unravelling host-virus interactions and dynamics of vaccine induced immune response

“…Predictive correlates that can be identified prior to vaccination are emerging in systems vaccinology studies. The first systems biological studies to dissect human vaccine-induced responses utilised the yellow fever vaccine, YF-17D (Morrison and Katze, 2015) (Xue and Miller-Jensen, 2012). Both CD8+ T cell and B cell signatures identified in microarray profiles were correlated with protective cell-mediated and antibody responses, thus providing predictive signatures.…”

“…Transcription factor XBP-1, found to be up regulated, which is necessary for the terminal differentiation of antibody-forming plasma cells, in RNA from sorted B cells, but not from PBMC, after TIV vaccination Reimold et al, 2001). Several recent studies have attempted to model the dynamic host immune responses to different viruses (Hancioglu et al, 2007;Tchitchek et al, 2013;Morrison and Katze, 2015;Storey et al, 2005;Liquet et al, 2012;Wang et al, 2009;Law et al, 2013;Josset et al, 2013;Bonneau, 2008). Hyperspectral cytometry is an emerging technology for single-cell analysis that combines ultrafast optical spectroscopy and flow cytometry.…”

“…Subsequent analysis of modelbased predictions using siRNA knockdown studies or knock-out animal models relate model findings to infection phenotypes and disease outcome in these experimental systems, refining models and driving further predictions (Tisoncik and Katze, 2010). More recently, systems biology is being applied to vaccinology, with the goal of understanding the mechanisms by which vaccines stimulate protective immunity, and predicting the immunogenicity or efficacy of vaccines (Morrison and Katze, 2015;Law et al, 2013;Josset et al, 2013;Chakrabarti et al, 2010;De Backer et al, 2010). Several recent studies have attempted to model the dynamic host immune responses to different viruses (Hancioglu et al, 2007;Tchitchek et al, 2013;Morrison and Katze, 2015;Storey et al, 2005;Liquet et al, 2012;Wang et al, 2009;Law et al, 2013;Josset et al, 2013;Bonneau, 2008).…”

“…More recently, systems biology is being applied to vaccinology, with the goal of understanding the mechanisms by which vaccines stimulate protective immunity, and predicting the immunogenicity or efficacy of vaccines (Morrison and Katze, 2015;Law et al, 2013;Josset et al, 2013;Chakrabarti et al, 2010;De Backer et al, 2010). Several recent studies have attempted to model the dynamic host immune responses to different viruses (Hancioglu et al, 2007;Tchitchek et al, 2013;Morrison and Katze, 2015;Storey et al, 2005;Liquet et al, 2012;Wang et al, 2009;Law et al, 2013;Josset et al, 2013;Bonneau, 2008). Systems biology in a nutshell can be useful in understanding differences in resistance/susceptibility to a particular disease in different species, identifying disease markers, identifying early markers of infection, prediction of the vaccine efficacy, identifying potential antiviral targets and understanding molecular mechanisms of the host-virus interactions (Chakrabarti et al, 2010;Josset et al, 2013).…”

Targeting the pro‐inflammatory factor CCL2 (MCP‐1) with Bindarit for influenza A (H7N9) treatment

“…Most patients infected with H7N9 experienced severe respiratory illness, such as pneumonia (97.3%) and acute respiratory distress syndrome (71.2%), leading to high rates of intensive care unit admissions 4 . The mortality rate attributed to influenza H7N9 infection in human is >38%, with 175 deaths from 450 confirmed cases reported within a 20‐month period 5 . No evidence of sustained human‐to‐human transmission of H7N9 has been recorded.…”