[HTML][HTML] Type I interferon inhibits antibody responses induced by a chimpanzee adenovirus vector

SE Hensley, AS Cun, W Giles-Davis, Y Li, Z Xiang… - Molecular Therapy, 2007 - cell.com
SE Hensley, AS Cun, W Giles-Davis, Y Li, Z Xiang, MO Lasaro, BRG Williams, RH Silverman…
Molecular Therapy, 2007cell.com
Recent studies have indicated that type I interferon (IFN) enhances antibody responses and
promotes isotype switching. In this study, we analyzed the role of type I IFN signaling during
the generation of transgene product-specific antibody responses elicited by recombinant
adenovirus (Ad) vectors. A vector derived from a human Ad serotype (AdHu5) induced low
levels of type I IFN following infection of dendritic cells (DCs) and stimulated normal
transgene product-specific antibody responses in mice that have a defective type I IFN …
Recent studies have indicated that type I interferon (IFN) enhances antibody responses and promotes isotype switching. In this study, we analyzed the role of type I IFN signaling during the generation of transgene product-specific antibody responses elicited by recombinant adenovirus (Ad) vectors. A vector derived from a human Ad serotype (AdHu5) induced low levels of type I IFN following infection of dendritic cells (DCs) and stimulated normal transgene product-specific antibody responses in mice that have a defective type I IFN receptor (IFNAR−/−). A vector derived from a chimpanzee Ad serotype (AdC68) induced very high levels of type I IFN following infection of DCs, and surprisingly, primed stronger transgene product-specific antibody responses in IFNAR−/− mice compared to wild-type mice. The increased antibody response in IFNAR−/− mice vaccinated with the AdC68 vector was mainly due to the generation of IgG1 antibodies that were not elicited in wild-type mice. The induction of IgG1 antibodies correlated with an increase in transgene product expression in IFNAR−/− mice and was not associated with an increase in T helper 2 responses. We conclude that type I IFN, when induced at high levels, can downregulate transgene product expression of Ad vectors and inhibit the formation of optimal antibody responses.
cell.com