title: Immunological adjuvants and their modes of action.
abstract: New adjuvant formulations contain a vehicle, which carries antigens to antigen-presenting cells. Examples of vehicles are liposomes, immune-stimulating complexes and microfluidized squalene-in-water emulsions. Adjuvant formulations may contain immunomodulators, which augment cytokine production, such as a synthetic muramyl dipeptide analog or monophosphoryl lipid A. In a primary cascade of cytokine production at the site of antigen + adjuvant injection, TNF-alpha promotes the migration of dendritic cells (DC) to lymphoid tissues while GM-CSF accelerates the differentiation of DC into efficient presenters of antigens to T cells. Adjuvants also up-regulate a secondary cascade of cytokines in lymphoid tissues responding to antigenic stimulation: IL-12 augments the production of IFN-gamma, which favors the production of antibodies of protective isotypes (IgG2a in the mouse). Thus adjuvants can regulate immune responses qualitatively as well as quantitatively. Adjuvant formulations can also activate complement, generating C3d, which binds CD21 on follicular dendritic cells (FDC) and B cells. FDC targeting favors the generation of B lymphocyte memory, which is important for vaccination.
authors.affiliation: Dawa Corporation, Belmont, CA 94002, USA.
authors.forename: A C
authors.initials: AC
authors.lastname: Allison
mesh_terms: D000119:Acetylmuramyl-Alanyl-Isoglutamine / Q000276:immunology / Q000494:pharmacology; D000276:Adjuvants, Immunologic / Q000145:classification / Q000494:pharmacology*; D017607:Aluminum Compounds / Q000494:pharmacology; D000818:Animals; D000917:Antibody Formation / Q000187:drug effects; D000938:Antigen-Presenting Cells / Q000187:drug effects / Q000276:immunology; D000941:Antigens / Q000276:immunology; D003167:Complement Activation / Q000187:drug effects; D016207:Cytokines / Q000096:biosynthesis; D003713:Dendritic Cells / Q000276:immunology / Q000378:metabolism; D004655:Emulsions; D006801:Humans; D016882:ISCOMs / Q000494:pharmacology; D007111:Immunity, Cellular / Q000187:drug effects; D007070:Immunoglobulin A / Q000096:biosynthesis; D007132:Immunoglobulin Isotypes / Q000096:biosynthesis / Q000276:immunology; D008050:Lipid A / Q000031:analogs & derivatives / Q000276:immunology / Q000494:pharmacology; D008081:Liposomes / Q000494:pharmacology; D051379:Mice; D009092:Mucous Membrane / Q000187:drug effects / Q000276:immunology; D012503:Saponins / Q000494:pharmacology; D012756:Sheep; D014612:Vaccines
chemical_list: D000276:Adjuvants, Immunologic; D017607:Aluminum Compounds; D000941:Antigens; D016207:Cytokines; D004655:Emulsions; D016882:ISCOMs; D007070:Immunoglobulin A; D007132:Immunoglobulin Isotypes; D008050:Lipid A; D008081:Liposomes; D012503:Saponins; D014612:Vaccines; D000119:Acetylmuramyl-Alanyl-Isoglutamine; C048436:monophosphoryl lipid A