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-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-alpha (TNF-alpha), but no IL-10, IL-12, or IL-1alpha. Parental dengue viruses induced a similar array of cytokines, but more TNF-alpha, 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.
Deauvieau
Florence
F
Research Department, Sanofi Pasteur, Marcy l'Etoile, France.
Sanchez
Violette
V
Balas
Claire
C
Kennel
Audrey
A
DE Montfort
Aymeric
A
Lang
Jean
J
Guy
Bruno
B
D015815:Cell Adhesion Molecules / Q000378:metabolism; D016207:Cytokines / Q000378:metabolism; D003713:Dendritic Cells / Q000276:immunology* / Q000821:virology*; D003715:Dengue / Q000276:immunology*; D053059:Dengue Vaccines / Q000009:adverse effects / Q000276:immunology*; D005786:Gene Expression Regulation; D006801:Humans; D007113:Immunity, Innate / Q000276:immunology*; D037181:Lectins, C-Type / Q000378:metabolism; D011956:Receptors, Cell Surface / Q000378:metabolism; D015004:Yellow Fever / Q000276:immunology*; D022341:Yellow Fever Vaccine / Q000276:immunology*; D000099215:DC-Specific ICAM-3 Grabbing Nonintegrin
D015815:Cell Adhesion Molecules; D016207:Cytokines; D053059:Dengue Vaccines; D037181:Lectins, C-Type; D011956:Receptors, Cell Surface; D022341:Yellow Fever Vaccine; D000099215:DC-Specific ICAM-3 Grabbing Nonintegrin