title: Increased potency of Fc-receptor-targeted antigens.
abstract: A major challenge for using native and modified T cell epitopes to induce or suppress immunity relates to achieving efficient uptake and processing by antigen-presenting cells (APC) in vivo. IgG Fc receptors, which are expressed constitutively by professional APC including monocytes and dendritic cells, have long been known to mediate antigen uptake in a manner leading to efficient T cell activation. We have previously demonstrated enhanced presentation of antigenic and antagonistic peptides 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 literature suggesting that CD64-targeted antigens are likely to be effective in vivo, and present data demonstrating enhanced immunogenicity in CD64 transgenic mice of a fusion protein that combines the specificities of HIV gp120 and the humanized anti-CD64 monoclonal antibody H22. Overall, these studies suggest that targeting antigens to CD64 represents an effective approach to enhancing the effectiveness of vaccines in vivo.
authors.affiliation: Department of Physiology, Dartmouth-Hitchcock Medical Center, Lebanon, NH 03756, USA. paul.guyre@dartmouth.edu
authors.forename: P M
authors.initials: PM
authors.lastname: Guyre
authors.forename: R F
authors.initials: RF
authors.lastname: Graziano
authors.forename: J
authors.initials: J
authors.lastname: Goldstein
authors.forename: P K
authors.initials: PK
authors.lastname: Wallace
authors.forename: P M
authors.initials: PM
authors.lastname: Morganelli
authors.forename: K
authors.initials: K
authors.lastname: Wardwell
authors.forename: A L
authors.initials: AL
authors.lastname: Howell
mesh_terms: D000818:Animals; D000938:Antigen-Presenting Cells / Q000276:immunology*; D000941:Antigens / Q000276:immunology*; D003713:Dendritic Cells / Q000276:immunology; D006801:Humans; D008213:Lymphocyte Activation / Q000276:immunology*; D008264:Macrophages / Q000276:immunology; D051379:Mice; D009000:Monocytes / Q000276:immunology; D011961:Receptors, Fc / Q000276:immunology*; D013601:T-Lymphocytes / Q000276:immunology; D014612:Vaccines / Q000276:immunology
chemical_list: D000941:Antigens; D011961:Receptors, Fc; D014612:Vaccines