In this report, we demonstrate that immunization of mice i.n. Furthermore, recent studies have demonstrated Ag-containing DCs administered i.n., like Ag-containing peripheral DCs, migrate to lymphoid tissues. immunization is less invasive and stimulates strong parenteral and mucosal immune responses. Importantly, while parenteral immunization generally utilizes needle injection and is not optimal for stimulating mucosal immunity, i.n. Thus, we hypothesized that the ability of ex vivo Ag-pulsed DCs to induce immunity/protection could be significantly enhanced by pulsing DCs with FcγR-targeted Ag administered i.n. The latter involves enhanced Ag binding to DCs, DC maturation, Ag processing/presentation by DCs, and i Ft trafficking to lymphoid tissues. tularensis (i Ft) Ag can induce enhanced protection against Ft challenge, when targeted to FcγRs as mAb-i Ft complexes (ICs) administered intranasally (i.n.). In this regard, studies from our laboratory have demonstrated that inactivated F. Consistent with these observations, engagement of FcγRs can induce DC maturation, a key event required for Ag processing and presentation to T cells. Furthermore, numerous studies, including our own, have demonstrated that targeting Ag to Fcγ receptors (FcγRs) on Ag presenting cells (APCs), can enhance humoral and cellular immunity and protection against infectious diseases and cancer. This has lead to studies focused on DC-based vaccines against cancer and infectious diseases including HIV-1 and influenza. Specifically, DCs are highly efficient at taking up, processing, and presenting antigens (Ags) to naïve T cells. Thus, this represents a simple and less invasive strategy for increasing the potency of ex vivo-pulsed DC vaccines against chronic infectious diseases and cancer.ĭendritic cells (DCs) play a central role in generating immunity to infection. In conclusion, targeting Ag ex vivo to FcγR on DCs provides a method for enhanced Ag loading of DCs ex vivo, thereby reducing the amount of Ag required, while also avoiding the inhibitory impact of FcγRIIB. However, the inhibitory FcγRIIB had no impact on this enhancement. Increased protection correlated with increased i Ft loading on the BMDC surface as a consequence of FcγR targeting. Intranasal administration of mAb-i Ft-pulsed BMDCs enhanced humoral and cellular immune responses, as well as protection against Ft live vaccine strain (LVS) challenge. In this study, bone marrow-derived DCs (BMDCs) were pulsed ex vivo with i Ft or mAb-i Ft ICs. Therefore, using i Ft Ag as a model immunogen, we sought to determine if ex vivo targeting of i Ft to FcγR on DCs would enhance the potency of i.n. Ft is the causative agent of tularemia, a debilitating disease of humans and other mammals and a category A biothreat agent for which there is no approved vaccine. tularensis ( Ft) infectious disease vaccine model have demonstrated that targeting immunogens to FcγR via intranasal (i.n.) administration of monoclonal antibody (mAb)-inactivated Ft (i Ft) immune complexes (ICs) enhances protection against Ft challenge. Studies have also demonstrated that targeting Ags to Fcγ receptors (FcγR) on Ag presenting cells can enhance humoral and cellular immunity in vitro and in vivo. Administration of Ag-pulsed DCs is also an effective strategy for enhancing immunity to tumors and infectious disease organisms. Dendritic cells (DCs) play a critical role in the generation of adaptive immunity via the efficient capture, processing, and presentation of antigen (Ag) to naïve T cells.
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