title: Antigen depot is not required for alum adjuvanticity.
abstract: Alum adjuvants have been in continuous clinical use for more than 80 yr. While the prevailing theory has been that depot formation and the associated slow release of antigen and/or inflammation are responsible for alum enhancement of antigen presentation and subsequent T- and B-cell responses, this has never been formally proven. To examine antigen persistence, we used the chimeric fluorescent protein EαGFP, which allows assessment of antigen presentation in situ, using the Y-Ae antibody. We demonstrate that alum and/or CpG adjuvants induced similar uptake of antigen, and in all cases, GFP signal did not persist beyond 24 h in draining lymph node antigen-presenting cells. Antigen presentation was first detectable on B cells within 6-12 h of antigen administration, followed by conventional dendritic cells (DCs) at 12-24 h, then finally plasmacytoid DCs at 48 h or later. Again, alum and/or CpG adjuvants did not have an effect on the magnitude or sequence of this response; furthermore, they induced similar antigen-specific T-cell activation in vivo. Notably, removal of the injection site and associated alum depot, as early as 2 h after administration, had no appreciable effect on antigen-specific T- and B-cell responses. This study clearly rules out a role for depot formation in alum adjuvant activity.
authors: Institute of Infection, Immunity and Inflammation, Sir Graeme Davies Bldg., 120 University Ave., University of Glasgow, Glasgow, G12 8TA UK.
authors: Sharon
authors: S
authors: Hutchison
authors: Robert A
authors: RA
authors: Benson
authors: Vivienne B
authors: VB
authors: Gibson
authors: Abigail H
authors: AH
authors: Pollock
authors: Paul
authors: P
authors: Garside
authors: James M
authors: JM
authors: Brewer
mesh_terms: D000276:Adjuvants, Immunologic / Q000494:pharmacology; D000534:Alum Compounds / Q000494:pharmacology*; D000818:Animals; D017951:Antigen Presentation / Q000187:drug effects* / Q000276:immunology; D000938:Antigen-Presenting Cells / Q000187:drug effects* / Q000276:immunology / Q000378:metabolism; D000941:Antigens / Q000008:administration & dosage / Q000276:immunology* / Q000378:metabolism; D001402:B-Lymphocytes / Q000187:drug effects / Q000276:immunology / Q000378:metabolism; D003713:Dendritic Cells / Q000187:drug effects / Q000276:immunology / Q000378:metabolism; D005260:Female; D005434:Flow Cytometry; D008198:Lymph Nodes / Q000187:drug effects / Q000276:immunology / Q000378:metabolism; D008213:Lymphocyte Activation / Q000187:drug effects / Q000276:immunology; D051379:Mice; D008807:Mice, Inbred BALB C; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D009838:Oligodeoxyribonucleotides / Q000494:pharmacology; D010047:Ovalbumin / Q000008:administration & dosage / Q000276:immunology / Q000493:pharmacokinetics; D013601:T-Lymphocytes / Q000187:drug effects / Q000276:immunology / Q000378:metabolism; D013997:Time Factors
chemical_list: D000276:Adjuvants, Immunologic; D000534:Alum Compounds; D000941:Antigens; C408982:CPG-oligonucleotide; D009838:Oligodeoxyribonucleotides; C041524:aluminum sulfate; D010047:Ovalbumin