The Canarypox-virus vaccine vector ALVAC triggers the release of IFN-γ 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)-γ. Immuno-depletion of NK cells prior to ALVAC immunisation abrogated IFN-γ production indicating that they are the main cellular source of early IFN-γ 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-γ, DC activation and chemokine secretion.