INCREASED POTENCY OF FC-RECEPTOR-TARGETED ANTIGENS

A major challenge for using native and modified T cell epitopes to ind uce or suppress immunity relates to achieving efficient uptake and pro cessing by antigen-pre senting cells (APC) in vivo. IgG Fc receptors, which are expressed constitutively by professional APC including monoc ytes and dendritic cells, have long been known to mediate antigen upta ke in a manner leading to efficient T cell activation. We have previou sly demonstrated enhanced presentation of antigenic and antagonistic p eptides by targeting them to the type I Fc receptor for IgG (Fc gamma RI, CD64) on human monocytes. In the present report we review the lite rature suggesting that CD64-targeted antigens are likely to be effecti ve in vivo, and present data demonstrating enhanced immunogenicity in CD64 transgenic mice of a fusion protein that combines the specificiti es of HIV gp120 and the humanized anti-CD64 monoclonal antibody H22. O verall, these studies suggest that targeting antigens to CD64 represen ts an effective approach to enhancing the effectiveness of vaccines in vivo.