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Improving Vaccination Via DC Targeting

Dendritic cells capture antigens and present them to cognate T cells to initiate the cascade of cellular events ultimately leading to effective immunity. However, antigen capture by DCs alone will not result in T cell activation unless a "maturation" stimulus is provided to the DC to induce co-stimulatory molecules. IgG immune complexes can provide this maturation stimulus if the inhibitory constraints of FcRIIB are abrogated on immature DCs. Effective vaccination thus entails the targeting of antigens to dendritic cells and the maturation of these DCs to mediate T cell activation. A research program is in progress to investigate the potential of this approach by targeting HIV antigens to DC by creating fusions between gp120 and an anti-Dc antibodiy, DEC 205. The maturation stimulus is provided by modifying the Fc domain of this antibody to selectively engage the activation FcR expressed on immature DCs. This approach will simultaneously deliver both antigen and a maturation signal to immature DCs, thereby accomplishing in a single step the dual goals of effective DC mediated vaccination.

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