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¹ Laboratoire d'immunologie, Centre de Recherche du Centre Hospitalier de l'Université de Montréal (CR-CHUM) Saint-Luc, Montréal, Québec, H2X 1P1, Canada
² Laboratoire d'immunologie, Département de microbiologie et d'immunologie, ³ INSERM U743, CR-CHUM, Université de Montréal, Québec H2X 1P1, Canada
⁴ VaxDesign Corporation, Orlando, FL 32826
⁵ Division of Immunology and Allergy, Department of Medicine, Centre Hospitalier Universitaire Vaudois, University of Lausanne, 1011 Lausanne, Switzerland
⁶ Travel Medicine and Vaccination Unit, Policlinique Médicale Universitaire, 1011 Lausanne, Switzerland
⁷ Emory Vaccine Center, Emory University School of Medicine, Atlanta, GA 30322
⁸ Canadian Network for Vaccines and Immunotherapeutics, Montréal, Québec, H3X 2H9, Canada
⁹ Biologics and Genetic Therapies Directorate, Health Canada, Tunney's Pasture, Ottawa, Ontario, K1A 0K9, Canada
¹⁰ Toronto General Research Institute, University Health Network, Toronto, Ontario M5G 2M9, Canada
¹¹ Biosystemix, Ltd., Sydenham, Ontario K0H 2T0, Canada
¹² BD Biosciences, San Diego, CA 92121
¹³ Aventis Pasteur, Ltd., Toronto, Ontario, M2R 3T4, Canada
¹⁴ Department of Microbiology and Immunology, McGill University, Montréal, Québec, H3A 2B4, Canada

CORRESPONDENCE Rafick-Pierre Sékaly: rafick-pierre.sekaly{at}umontreal.ca

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.

N. Kettaf and B.R. Angermann and E.K. Haddad and R.-P. Sékaly contributed equally to this paper.

© 2008 Gaucher et al. This article is distributed under the terms of an Attribution–Noncommercial–Share Alike–No Mirror Sites license for the first six months after the publication date (see http://www.jem.org/misc/terms.shtml). After six months it is available under a Creative Commons License (Attribution–Noncommercial–Share Alike 3.0 Unported license, as described at http://creativecommons.org/licenses/by-nc-sa/3.0/).

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