Yellow fever vaccine induces integrated multilineage and polyfunctional immune responses

Denis Gaucher, René Therrien, Nadia Kettaf, Bastian R. Angermann, Geneviéve Boucher, Abdelali Filali-Mouhim, Janice M. Moser, Riyaz S. Mehta, Donald R. Drake, Erika Castro, Rama Akondy, Aline Rinfret, Bader Yassine-Diab, Elias A. Said, Younes Chouikh, Mark J. Cameron, Robert Clum, David Kelvin, Roland Somogyi, Larry D. GrellerRobert S. Balderas, Peter Wilkinson, Giuseppe Pantaleo, Jim Tartaglia, Elias K. Haddad, Rafick Pierre Sekaly

Research output: Contribution to journalArticle

402 Citations (Scopus)

Abstract

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.

Original languageEnglish
Pages (from-to)3119-3131
Number of pages13
JournalJournal of Experimental Medicine
Volume205
Issue number13
DOIs
Publication statusPublished - Dec 22 2008

ASJC Scopus subject areas

  • Immunology
  • Immunology and Allergy
  • Medicine(all)

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    Gaucher, D., Therrien, R., Kettaf, N., Angermann, B. R., Boucher, G., Filali-Mouhim, A., Moser, J. M., Mehta, R. S., Drake, D. R., Castro, E., Akondy, R., Rinfret, A., Yassine-Diab, B., Said, E. A., Chouikh, Y., Cameron, M. J., Clum, R., Kelvin, D., Somogyi, R., ... Sekaly, R. P. (2008). Yellow fever vaccine induces integrated multilineage and polyfunctional immune responses. Journal of Experimental Medicine, 205(13), 3119-3131. https://doi.org/10.1084/jem.20082292