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.
Publication types
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Research Support, N.I.H., Extramural
MeSH terms
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Adaptor Proteins, Vesicular Transport / genetics
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Adaptor Proteins, Vesicular Transport / metabolism
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Adjuvants, Immunologic*
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Animals
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Antibody Formation*
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Antigens, T-Independent / immunology
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B-Lymphocytes / immunology*
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Cell Wall Skeleton / immunology
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Cord Factors / immunology
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Freund's Adjuvant / immunology
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Haptens
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Hemocyanins / immunology
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Immunity, Innate
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Immunization
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Immunization, Secondary
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Immunoglobulins / blood
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Ligands
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Lipid A / analogs & derivatives
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Lipid A / immunology
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Lipopolysaccharides / immunology
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Lymphocyte Activation
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Mice
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Mice, Inbred C57BL
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Myeloid Differentiation Factor 88 / genetics
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Myeloid Differentiation Factor 88 / metabolism
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Picrates / immunology
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Signal Transduction*
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T-Lymphocytes / immunology
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Toll-Like Receptors / immunology*
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Toll-Like Receptors / metabolism
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Vaccines / immunology
Substances
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Adaptor Proteins, Vesicular Transport
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Adjuvants, Immunologic
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Antigens, T-Independent
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Cell Wall Skeleton
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Cord Factors
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Haptens
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Immunoglobulins
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Ligands
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Lipid A
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Lipopolysaccharides
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Myd88 protein, mouse
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Myeloid Differentiation Factor 88
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Picrates
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Ribi adjuvant
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TICAM-1 protein, mouse
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Toll-Like Receptors
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Vaccines
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trinitrophenyl keyhole limpet hemocyanin
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Freund's Adjuvant
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Hemocyanins
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picric acid