Increased potency of Fc-receptor-targeted antigens |
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Authors: | P M Guyre Robert F Graziano Joel Goldstein Paul K Wallace Peter M Morganelli Kathleen Wardwell Alexandra L Howell |
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Institution: | (1) Department of Physiology, 740W Borwell Building, 1 Medical Center Drive, Dartmouth-Hitchcock Medical Center, Lebanon, NH 03756, USA Tel. +1 603 650 8150; Fax +1 603 650 6130 e-mail: paul.guyre@dartmouth.edu, LB;(2) Department of Microbiology, Dartmouth-Hitchcock Medical Center, Lebanon, NH 03756-0001, USA, LB;(3) Medarex Inc., 1545 Route 22 East, Annadale, NJ 08801-0992, USA, US |
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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 (FcγRI, 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.
Accepted: 14 October 1997 |
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Keywords: | Fc receptor Vaccine Antigen presentation CD64 |
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