HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS		QUICK SEARCH:   [advanced] Author: Keyword(s): Year:  Vol:  Page:

This Article Full Text Full Text (PDF) Alert me when this article is cited Alert me if a correction is posted Citation Map Services Similar articles in this journal Similar articles in ISI Web of Science Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by DEAUVIEAU, F. Articles by GUY, B. Search for Related Content PubMed PubMed Citation Articles by DEAUVIEAU, F. Articles by GUY, B. Related Collections Yellow Fever Immunology Vaccine Dengue

INNATE IMMUNE RESPONSES IN HUMAN DENDRITIC CELLS UPON INFECTION BY CHIMERIC YELLOW-FEVER DENGUE VACCINE SEROTYPES 1–4

Dengue infection is an important public health issue worldwide. The ChimeriVax^TM-Dengue (CYD) vaccine uses yellow fever (YF) 17D vaccine as a live vector. Dendritic cells (DCs) play a key role in initiating immune responses and could be an important primary target of dengue infection. We investigated in vitro the consequences of CYD infection of DCs on their activation/maturation and cytokine production. In CYD-infected DCs, we observed an up-regulation of HLA-DR, CD80, CD86, and CD83. Cells exposed to CYD secreted type I interferons, monocyte chemoattractant protein 1 (MCP-1)/CC chemokine ligand 2 (CCL-2), interleukin-6 (IL-6), and low amounts of tumor necrosis factor- (TNF-), but no IL-10, IL-12, or IL-1. Parental dengue viruses induced a similar array of cytokines, but more TNF-, less IL-6, and less MCP-1/CCL-2 than induced by CYD. Chimeras thus induced DCs maturation and a controlled response accompanied by limited inflammatory cytokine production and consistent expression of anti-viral interferons, in agreement with clinical observations of safety and immunogenicity.

Received February 15, 2006. Accepted for publication September 26, 2006.

Acknowledgments: We thank G. Marsh for critical help in the preparation of this manuscript, N. Burdin for constant support and helpful discussions, C. Fournier and C. Droy for providing the CYDs vaccines, V. Barban and F. Pradezynski for performing the viral quantifications in cell supernatants and for helpful discussions, and F. Guirakhoo (Acambis, Cambridge, MA) for providing the parental dengue virus strains.

Financial support: This study was supported by sanofi pasteur.

Disclosure: The authors wish to report that their company has an exclusive license to develop the ChimeriVax^TM-dengue vaccines initially developed by Acambis (Cambridge, MA) that are used in this study. This statement is made in the interest of full disclosure and not because the authors consider this to be a conflict of interest.

^* Address correspondence to Bruno Guy, Research Department, sanofi pasteur, Campus Merieux, 1541 Avenue Marcel Merieux, 69280 Marcy l’Etoile, France. E-mail: bruno.guy{at}sanofipasteur.com

Authors’ address: Florence Deauvieau, Violette Sanchez, Claire Balas, Audrey Kennel, Aymeric de Montfort, Jean Lang, and Bruno Guy, Research Department, sanofi pasteur, Campus Merieux, 1541 Avenue Marcel Merieux, 69280 Marcy l’Etoile, France, E-mail: bruno.guy{at}sanofipasteur.com.

This article has been cited by other articles:

				M. C. Silva, A. Guerrero-Plata, F. D. Gilfoy, R. P. Garofalo, and P. W. Mason Differential Activation of Human Monocyte-Derived and Plasmacytoid Dendritic Cells by West Nile Virus Generated in Different Host Cells J. Virol., December 15, 2007; 81(24): 13640 - 13648. [Abstract] [Full Text] [PDF]