Role of Type I IFN signaling in induction of humoral response induced by viral vectored vaccines

Abstract

Abstract HIV vaccine candidates based on different viral vectors (adenovirus and poxvirus) have been tested in human efficacy trials but were associated with distinct vaccine outcomes. In particular, the vaccine regimen tested in RV144 trial involving poxvirus (ALVAC) vectored HIV vaccine provided a modest protection, which was associated with vaccine-induced HIV envelope-specific IgG antibody response. Our recent study examining host innate immunity to different viral vectors demonstrated that distinct from Ad5, the poxvirus vector can stimulate strong type-I interferon (IFN) response. In this study, we aimed to understand the impact of type I IFN signaling on generation of HIV vaccine-specific humoral immune response induced by poxvirus vectored vaccines. Here we used poxvirus vectored vaccine (MVA-HIV) that is capable of triggering type-I IFN response as a vaccination model. Prime-boost immunization of MVA-HIV in mice demonstrated that compared to wildtype mice, type I IFN receptor-deficient mice produced significantly lower levels of total and HIV gp120-specific IgG after vaccination. Consistent with the antibody response, type-I IFN signaling deficiency also resulted in lower levels of memory B cells as compared to those in WT mice, although the levels of germinal center B cells were comparable between WT and KO mice. Furthermore, our study also provided evidence that type-I IFN signaling may be involved in the generation of vaccine-specific CD4 T-cell response, including induction of HIV gp120-specific T follicular helper (Tfh) cells. Altogether, our data suggest that type I IFN signaling plays an important role in viral vector vaccination by promoting the generation of vaccine-specific humoral response and Tfh response.