TY - JOUR
T1 - Yellow fever vaccine induces integrated multilineage and polyfunctional immune responses
AU - Gaucher, Denis
AU - Therrien, René
AU - Kettaf, Nadia
AU - Angermann, Bastian R.
AU - Boucher, Geneviéve
AU - Filali-Mouhim, Abdelali
AU - Moser, Janice M.
AU - Mehta, Riyaz S.
AU - Drake, Donald R.
AU - Castro, Erika
AU - Akondy, Rama
AU - Rinfret, Aline
AU - Yassine-Diab, Bader
AU - Said, Elias A.
AU - Chouikh, Younes
AU - Cameron, Mark J.
AU - Clum, Robert
AU - Kelvin, David
AU - Somogyi, Roland
AU - Greller, Larry D.
AU - Balderas, Robert S.
AU - Wilkinson, Peter
AU - Pantaleo, Giuseppe
AU - Tartaglia, Jim
AU - Haddad, Elias K.
AU - Sekaly, Rafick Pierre
PY - 2008/12/22
Y1 - 2008/12/22
N2 - 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.
AB - 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.
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U2 - 10.1084/jem.20082292
DO - 10.1084/jem.20082292
M3 - Article
C2 - 19047440
AN - SCOPUS:59649129816
SN - 0022-1007
VL - 205
SP - 3119
EP - 3131
JO - Journal of Experimental Medicine
JF - Journal of Experimental Medicine
IS - 13
ER -