Systems biology approach predicts immunogenicity of the yellow fever vaccine in humans

By T. Querec, Rama S. Akondy, Eva K. Lee, W. Cao, H. Nakaya, D. Teuwen, A. Pirani, K. Gernert, Jiusheng Deng, Bruz Marzolf and 10 more. Nature Immunology, 2008

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A major challenge in vaccinology is to prospectively determine vaccine efficacy. Here we have used a systems biology approach to identify early gene 'signatures' that predicted immune responses in humans vaccinated with yellow fever vaccine YF-17D. Vaccination induced genes that regulate virus innate sensing and type I interferon production. Computational analyses identified a gene signature, including complement protein C1qB and eukaryotic translation initiation factor 2 alpha kinase 4—an orchestrator of the integrated stress response—that correlated with and predicted YF-17D CD8+ T cell responses with up to 90% accuracy in an independent, blinded trial. A distinct signature, including B cell growth factor TNFRS17, predicted the neutralizing antibody response with up to 100% accuracy. These data highlight the utility of systems biology approaches in predicting vaccine efficacy.

Subfields: Immunology, Molecular Biology, Public Health, Environmental and Occupational Health

View Paper: https://www.semanticscholar.org/paper/4bdea5e21da87fb930f8fb5cf9d9036678d7ca23

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Dean P. Jones

Citations in the corpus

From Vaccines to Memory and Back (2010, neutral): “…are present in the bone marrow and secrete antibodies in an antigen-independent fashion thus maintaining constant levels in serum and body fluids (Radbruch et al., 2006); recall responses are mediated by memory B cells that rapidly proliferate and differentiate in response to antigenic…”
Immunosenescence: molecular mechanisms and diseases (2023, methodology): “Using a systems biology approach to identify early gene signatures is pioneering work for predicting immune responses in humans.(223) Pulendran and colleagues conducted a series of clinical studies over three years to evaluate the responses to influenza vaccination in adults.”
Predicting Network Activity from High Throughput Metabolomics (2013, background): “The arrows point to the corresponding signals in plots of LC retention time (x-axis) vs m/z (y-axis), where a large peak is seen in YF17D sample but missing in Mock sample.”
Stereotypic Immune System Development in Newborn Children (2018, background): “Human systems immunology analyses have now revealed not only large interindividual variation in immune cells and in protein composition (Gaucher et al., 2008; Nakaya et al., 2015; Querec et al., 2009; Sobolev et al., 2016) but also a stability of phenotypes within individuals over the course of week”
Systems Biology of Seasonal Influenza Vaccination in Humans (2011, methodology): “This approach identified unique biomarkers (molecular signatures) that predicted the magnitude of the antigen-specific CD8 + T cell and antibody responses induced by YF-17D 6,7 , and the formulation of new hypotheses about the mechanism of action of this vaccine.”
Cancer immunotherapy via dendritic cells (2012, neutral): “A better understanding of how effective vaccines stimulate protective immune response”
Variation in the human immune system is largely driven by non-heritable influences (2015, background): “The vertebrate immune system consist of thousands of different components and the application of systems biology (Davis, 2008; Duffy et al., 2014; Li et al., 2013; Querec et al., 2009; Sekaly, 2008; Tsang et al., 2014) holds great promise as a way to understand the interactions between these during ”
Immunological mechanisms of vaccination (2011, background): “In this context, there are now increasing efforts to understand immune regulation from the point of view of systems biolog”