The Canarypox-virus vaccine vector ALVAC triggers the release of IFN-gamma by Natural Killer (NK) cells enhancing Th1 polarization.
We investigated the mechanism by which ALVAC activates innate immunity. Combining ALVAC with protein antigens significantly augmented antigen-specific IgG2a responses; this was dependent on the presence of bioactive interferon (IFN)-gamma. Immuno-depletion of NK cells prior to ALVAC immunisation abrogated IFN-gamma production indicating that they are the main cellular source of early IFN-gamma in vivo. Murine bone-marrow derived dendritic cells (BMDCs) cultured in the presence of ALVAC secreted high levels of the chemokines CXCL10 and CCL2 and up-regulated expression of the maturation markers CD40, CD80 and CD86. Therefore, we conclude that ALVAC acts as an adjuvant through a mechanism requiring NK cell derived IFN-gamma, DC activation and chemokine secretion.
Ryan
Elizabeth J
EJ
Sanofi-Pasteur, Campus Mérieux, 1541 Avenue Marcel Mérieux, 69280 Marcy l'Etoile, France. Elizabeth.Ryan@ucd.ie
Harenberg
Anke
A
Burdin
Nicolas
N
D016915:AIDS Vaccines / Q000276:immunology*; D000818:Animals; D028121:Canarypox virus / Q000276:immunology*; D016764:Cell Polarity; D054357:Chemokine CXCL10; D019743:Chemokines, CXC / Q000502:physiology; D003713:Dendritic Cells / Q000276:immunology; D005260:Female; D016898:Interferon-alpha / Q000096:biosynthesis; D007371:Interferon-gamma / Q000096:biosynthesis*; D007694:Killer Cells, Natural / Q000276:immunology*; D051379:Mice; D008807:Mice, Inbred BALB C; D015398:Signal Transduction; D018417:Th1 Cells / Q000276:immunology*
D016915:AIDS Vaccines; D054357:Chemokine CXCL10; D019743:Chemokines, CXC; D016898:Interferon-alpha; D007371:Interferon-gamma