Interferon-β expressed by a rabies virus-based HIV-1 vaccine vector serves as a molecular adjuvant and decreases pathogenicity

Type I interferon is important in anti-viral responses and in coordinating the innate immune response. Here we explore the use of interferon-beta to adjuvant the response to a rabies virus (RV) vaccine vector expressing both HIV-1 Gag and IFN-beta. Viral load and immune responses of immunized mice were analyzed Over time. Our results indicate that the RV expressing IFN-beta (IFN(+)) is highly attenuated when compared to control RV and demonstrate that the expression of IFN-beta reduces Viral replication approximately 100-fold. Despite the decrease in replication, those mice immunized with the IFN(+) RV had a significantly greater number Of activated CD8+ T cells. The increased activation of CD8+ T cells was dependent oil IFN-beta signaling, as we saw no difference following infection of IFNAR-/- mice. Although mice immunized with IFN(+) have a greater primary immune response than controls, immunized mice that were challenged with vaccinia-expressing Gag had no significant difference in the number or functionality of CD8+ T cells. The increased CD8+ T cell activation in the presence of IFN-beta even with greatly reduced viral replication, indicates the beneficial effect of IFN-beta for the host. (C) 2008 Elsevier Inc. All Fights reserved.