Yellow fever vaccine induces integrated multilineage and polyfunctional immune responses.
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.
Gaucher
Denis
D
Laboratoire d'Immunologie, Centre de Recherche du Centre Hospitalier de l'Université de Montréal (CR-CHUM) Saint-Luc, Montréal, Québec, Canada.
Therrien
René
R
Kettaf
Nadia
N
Angermann
Bastian R
BR
Boucher
Geneviève
G
Filali-Mouhim
Abdelali
A
Moser
Janice M
JM
Mehta
Riyaz S
RS
Drake
Donald R
DR
Castro
Erika
E
Akondy
Rama
R
Rinfret
Aline
A
Yassine-Diab
Bader
B
Said
Elias A
EA
Chouikh
Younes
Y
Cameron
Mark J
MJ
Clum
Robert
R
Kelvin
David
D
Somogyi
Roland
R
Greller
Larry D
LD
Balderas
Robert S
RS
Wilkinson
Peter
P
Pantaleo
Giuseppe
G
Tartaglia
Jim
J
Haddad
Elias K
EK
Sékaly
Rafick-Pierre
RP
D001402:B-Lymphocytes / Q000166:cytology / Q000276:immunology; D049109:Cell Proliferation; D005434:Flow Cytometry; D020869:Gene Expression Profiling; D005786:Gene Expression Regulation / Q000276:immunology*; D053263:Gene Regulatory Networks; D006801:Humans; D055633:Immune System Phenomena; D007113:Immunity, Innate / Q000276:immunology*; D053583:Interleukin-1beta / Q000276:immunology; D016131:Lymphocyte Subsets / Q000276:immunology / Q000502:physiology; D013601:T-Lymphocytes / Q000166:cytology / Q000276:immunology; D014158:Transcription, Genetic; D014611:Vaccination; D022341:Yellow Fever Vaccine / Q000276:immunology*
D053583:Interleukin-1beta; D022341:Yellow Fever Vaccine