Yellow fever vaccine induces integrated multilineage and polyfunctional immune responses

By D. Gaucher, René Therrien, Nadia Kettaf, B. Angermann, G. Boucher, A. Filali‐Mouhim, J. Moser, R. Mehta, D. Drake, E. Castro and 16 more. Journal of Experimental Medicine, 2008

623 citations recorded by the source corpus.

Correlates of immune-mediated protection to most viral and cancer vaccines are still unknown. This impedes the development of novel vaccines to incurable diseases such as HIV and cancer. In this study, we have used functional genomics and polychromatic flow cytometry to define the signature of the immune response to the yellow fever (YF) vaccine 17D (YF17D) in a cohort of 40 volunteers followed for up to 1 yr after vaccination. We show that immunization with YF17D leads to an integrated immune response that includes several effector arms of innate immunity, including complement, the inflammasome, and interferons, as well as adaptive immunity as shown by an early T cell response followed by a brisk and variable B cell response. Development of these responses is preceded, as demonstrated in three independent vaccination trials and in a novel in vitro system of primary immune responses (modular immune in vitro construct [MIMIC] system), by the coordinated up-regulation of transcripts for specific transcription factors, including STAT1, IRF7, and ETS2, which are upstream of the different effector arms of the immune response. These results clearly show that the immune response to a strong vaccine is preceded by coordinated induction of master transcription factors that lead to the development of a broad, polyfunctional, and persistent immune response that integrates all effector cells of the immune system.

Subfields: Immunology, Infectious Diseases, Public Health, Environmental and Occupational Health

View Paper: https://www.semanticscholar.org/paper/376f2c1191457d10e73ac0f3d471f63d9fa509ad

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Citations in the corpus

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.”
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”
Exhaustion of tumor-specific CD8⁺ T cells in metastases from melanoma patients. (2011, result): “In contrast to vaccines consisting of synthetic molecules and inactivated pathogens, live vaccines (essentially vaccinia virus and yellow fever vaccine) can induce high T cell frequencies (42, 43) and efficient protection.”
Systems analysis of sex differences reveals an immunosuppressive role for testosterone in the response to influenza vaccination (2013, background): “In one study, results from public gene expression data (13) showed that many of the genes induced by a yellow fever vaccine were preferentially activated in females (14).”
Studying and modelling dynamic biological processes using time-series gene expression data (2012, background): “Instead, many such studies examine peripheral blood mononuclear cells 46,96,105 or other peripheral blood cells 9 as an approximation, owing to their accessibility.”
Cancer immunotherapy via dendritic cells (2012, neutral): “A better understanding of how effective vaccines stimulate protective immune response”
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”