title: Adjuvant-enhanced antibody responses in the absence of toll-like receptor signaling.
abstract: Innate immune signals mediated by Toll-like receptors (TLRs) have been thought to contribute considerably to the antibody-enhancing effects of vaccine adjuvants. However, we report here that mice deficient in the critical signaling components for TLR mount robust antibody responses to T cell-dependent antigen given in four typical adjuvants: alum, Freund's complete adjuvant, Freund's incomplete adjuvant, and monophosphoryl-lipid A/trehalose dicorynomycolate adjuvant. We conclude that TLR signaling does not account for the action of classical adjuvants and does not fully explain the action of a strong adjuvant containing a TLR ligand. This may have important implications in the use and development of vaccine adjuvants.
authors.affiliation: Department of Immunology, The Scripps Research Institute, La Jolla, CA 92037 USA.
authors.forename: Amanda L
authors.initials: AL
authors.lastname: Gavin
authors.forename: Kasper
authors.initials: K
authors.lastname: Hoebe
authors.forename: Bao
authors.initials: B
authors.lastname: Duong
authors.forename: Takayuki
authors.initials: T
authors.lastname: Ota
authors.forename: Christopher
authors.initials: C
authors.lastname: Martin
authors.forename: Bruce
authors.initials: B
authors.lastname: Beutler
authors.forename: David
authors.initials: D
authors.lastname: Nemazee
mesh_terms: D033942:Adaptor Proteins, Vesicular Transport / Q000235:genetics / Q000378:metabolism; D000276:Adjuvants, Immunologic; D000818:Animals; D000917:Antibody Formation; D000955:Antigens, T-Independent / Q000276:immunology; D001402:B-Lymphocytes / Q000276:immunology*; D017358:Cell Wall Skeleton / Q000276:immunology; D003311:Cord Factors / Q000276:immunology; D005620:Freund's Adjuvant / Q000276:immunology; D006241:Haptens; D006433:Hemocyanins / Q000276:immunology; D007113:Immunity, Innate; D007114:Immunization; D007117:Immunization, Secondary; D007136:Immunoglobulins / Q000097:blood; D008024:Ligands; D008050:Lipid A / Q000031:analogs & derivatives / Q000276:immunology; D008070:Lipopolysaccharides / Q000276:immunology; D008213:Lymphocyte Activation; D051379:Mice; D008810:Mice, Inbred C57BL; D053594:Myeloid Differentiation Factor 88 / Q000235:genetics / Q000378:metabolism; D010851:Picrates / Q000276:immunology; D015398:Signal Transduction; D013601:T-Lymphocytes / Q000276:immunology; D051193:Toll-Like Receptors / Q000276:immunology* / Q000378:metabolism; D014612:Vaccines / Q000276:immunology
chemical_list: D033942:Adaptor Proteins, Vesicular Transport; D000276:Adjuvants, Immunologic; D000955:Antigens, T-Independent; D017358:Cell Wall Skeleton; D003311:Cord Factors; D005620:Freund's Adjuvant; D006241:Haptens; D006433:Hemocyanins; D007136:Immunoglobulins; D008024:Ligands; D008050:Lipid A; D008070:Lipopolysaccharides; D053594:Myeloid Differentiation Factor 88; D010851:Picrates; D051193:Toll-Like Receptors; D014612:Vaccines; C507780:Myd88 protein, mouse; C075897:Ribi adjuvant; C476286:Ticam1 protein, mouse; C054401:trinitrophenyl keyhole limpet hemocyanin; C005858:picric acid