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Science 314 (5807): 1936-1938

Copyright © 2006 by the American Association for the Advancement of Science

Adjuvant-Enhanced Antibody Responses in the Absence of Toll-Like Receptor Signaling

Amanda L. Gavin,1 Kasper Hoebe,1 Bao Duong,1,2 Takayuki Ota,1 Christopher Martin,1,2 Bruce Beutler,1 David Nemazee1*

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.

1 Department of Immunology, The Scripps Research Institute, La Jolla, CA 92037 USA.
2 The Scripps Research Institute, Kellogg School of Science and Technology, Doctoral Program in Chemical and Biological Sciences, La Jolla, CA 92037, USA.

* To whom correspondence should be addressed. E-mail: nemazee{at}scripps.edu

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J. Immunol. 179, 6524-6535
   Abstract »    Full Text »    PDF »
Primary Development and Participation in a Foreign Antigen-Driven Immune Response of a Chromatin-Reactive B Cell Clonotype Are Not Influenced by TLR9 or Other MyD88-Dependent TLRs.
F. Coffey, X. Liu, and T. Manser (2007)
J. Immunol. 179, 6663-6672
   Abstract »    Full Text »    PDF »
Danger-free autoimmune disease in Aire-deficient mice.
D. H. D. Gray, I. Gavanescu, C. Benoist, and D. Mathis (2007)
PNAS 104, 18193-18198
   Abstract »    Full Text »    PDF »
Autoimmunity Stimulated by Adoptively Transferred Dendritic Cells Is Initiated by Both {alpha}beta and {gamma}{delta} T Cells but Does Not Require MyD88 Signaling.
D. A. Martin, K. Zhang, J. Kenkel, G. Hughes, E. Clark, A. Davidson, and K. B. Elkon (2007)
J. Immunol. 179, 5819-5828
   Abstract »    Full Text »    PDF »
Selective predisposition to bacterial infections in IRAK-4 deficient children: IRAK-4 dependent TLRs are otherwise redundant in protective immunity.
C.-L. Ku, H. von Bernuth, C. Picard, S.-Y. Zhang, H.-H. Chang, K. Yang, M. Chrabieh, A. C. Issekutz, C. K. Cunningham, J. Gallin, et al. (2007)
J. Exp. Med. 204, 2407-2422
   Abstract »    Full Text »    PDF »
Sustained antigen presentation can promote an immunogenic T cell response, like dendritic cell activation.
R. Obst, H.-M. van Santen, R. Melamed, A. O. Kamphorst, C. Benoist, and D. Mathis (2007)
PNAS 104, 15460-15465
   Abstract »    Full Text »    PDF »
Neisseria meningitidis PorB, a TLR2 Ligand, Induces an Antigen-Specific Eosinophil Recall Response: Potential Adjuvant for Helminth Vaccines?.
J. M. Burke, L. M. Ganley-Leal, A. Khatri, and L. M. Wetzler (2007)
J. Immunol. 179, 3222-3230
   Abstract »    Full Text »    PDF »
BAFF and MyD88 signals promote a lupuslike disease independent of T cells.
J. R. Groom, C. A. Fletcher, S. N. Walters, S. T. Grey, S. V. Watt, M. J. Sweet, M. J. Smyth, C. R. Mackay, and F. Mackay (2007)
J. Exp. Med. 204, 1959-1971
   Abstract »    Full Text »    PDF »
The Vaccine Adjuvant Monophosphoryl Lipid A as a TRIF-Biased Agonist of TLR4.
V. Mata-Haro, C. Cekic, M. Martin, P. M. Chilton, C. R. Casella, and T. C. Mitchell (2007)
Science 316, 1628-1632
   Abstract »    Full Text »    PDF »
TLR Agonists Selectively Promote Terminal Plasma Cell Differentiation of B Cell Subsets Specialized in Thymus-Independent Responses.
L. Genestier, M. Taillardet, P. Mondiere, H. Gheit, C. Bella, and T. Defrance (2007)
J. Immunol. 178, 7779-7786
   Abstract »    Full Text »    PDF »
Salmonella Induces a Switched Antibody Response without Germinal Centers That Impedes the Extracellular Spread of Infection.
A. F. Cunningham, F. Gaspal, K. Serre, E. Mohr, I. R. Henderson, A. Scott-Tucker, S. M. Kenny, M. Khan, K.-M. Toellner, P. J. L. Lane, et al. (2007)
J. Immunol. 178, 6200-6207
   Abstract »    Full Text »    PDF »
Viral induction of AID is independent of the interferon and the Toll-like receptor signaling pathways but requires NF-{kappa}B.
P. Gourzi, T. Leonova, and F. N. Papavasiliou (2007)
J. Exp. Med. 204, 259-265
   Abstract »    Full Text »    PDF »

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