Increased potency of Fc-receptor-targeted antigens.
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.
Guyre
P M
PM
Department of Physiology, Dartmouth-Hitchcock Medical Center, Lebanon, NH 03756, USA. paul.guyre@dartmouth.edu
Graziano
R F
RF
Goldstein
J
J
Wallace
P K
PK
Morganelli
P M
PM
Wardwell
K
K
Howell
A L
AL
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
D000941:Antigens; D011961:Receptors, Fc; D014612:Vaccines