Fc receptor-targeting of immunogen as a strategy for enhanced antigen loading, vaccination, and protection using intranasally-administered ex vivo antigen-pulsed dendritic cells (P4292)

Abstract

Abstract Dendritic cells play a critical role in the generation of an effective adaptive immune response. This is primarily due to their ability to capture, process, and present Ag to naïve T cells. Administration of Ag-pulsed DCs has proven to be an effective strategy for enhancing immunity to both tumors and infectious disease organisms. In addition, our own studies using an F. tularensis infectious disease vaccine model have demonstrated that targeting immunogens to FcγR via intranasal administration of inactivated F. tularensis-mAb complexes enhances protection against F. tularensis challenge. Therefore, we sought to determine if ex vivo targeting of Ag to FcγR would enhance the potency of intranasally administered Ag-pulsed DCs. In this study, bone marrow-derived DCs were pulsed ex vivo with inactivated F. tularensis alone or complexed to mAb. Immunization of mice, via intranasal injection of F. tularensis-mAb-pulsed DCs, enhanced humoral and cellular immune responses, as well as protection against F. tularensis infection. These observations correlated with increased loading of Ag on the DCs as a consequence of FcR targeting. Importantly, engagement of the inhibitory receptor FcγRIIB had no impact on this enhancement. In conclusion, targeting Ag ex vivo via FcγR on DCs provides a method for enhanced Ag loading of DCs, while bypassing the inhibitory impact of FcγRIIB. Thus, this represents an important strategy for increasing the potency of ex vivo-pulsed DC vaccines.