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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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   Abstract »    Full Text »    PDF »
Colonic Patches Direct the Cross-Talk Between Systemic Compartments and Large Intestine Independently of Innate Immunity.
S.-Y. Chang, H.-R. Cha, S. Uematsu, S. Akira, O. Igarashi, H. Kiyono, and M.-N. Kweon (2008)
J. Immunol. 180, 1609-1618
   Abstract »    Full Text »    PDF »
Ets-1 Regulates Plasma Cell Differentiation by Interfering with the Activity of the Transcription Factor Blimp-1.
S. A. John, J. L. Clements, L. M. Russell, and L. A. Garrett-Sinha (2008)
J. Biol. Chem. 283, 951-962
   Abstract »    Full Text »    PDF »
Interleukin-15 Increases Vaccine Efficacy through a Mechanism Linked to Dendritic Cell Maturation and Enhanced Antibody Titers.
K. U. Saikh, T. L. Kissner, S. Nystrom, G. Ruthel, and R. G. Ulrich (2008)
Clin. Vaccine Immunol. 15, 131-137
   Abstract »    Full Text »    PDF »
Receptor for Advanced Glycation End Products Expression on T Cells Contributes to Antigen-Specific Cellular Expansion In Vivo.
B. Moser, D. D. Desai, M. P. Downie, Y. Chen, S. F. Yan, K. Herold, A. M. Schmidt, and R. Clynes (2007)
J. Immunol. 179, 8051-8058
   Abstract »    Full Text »    PDF »
Agonists of Toll-Like Receptors 3, 4, 7, and 9 Are Candidates for Use as Adjuvants in an Outer Membrane Vaccine against Neisseria meningitidis Serogroup B.
F. Fransen, C. J. Boog, J. P. van Putten, and P. van der Ley (2007)
Infect. Immun. 75, 5939-5946
   Abstract »    Full Text »    PDF »
A protein associated with Toll-like receptor (TLR) 4 (PRAT4A) is required for TLR-dependent immune responses.
K. Takahashi, T. Shibata, S. Akashi-Takamura, T. Kiyokawa, Y. Wakabayashi, N. Tanimura, T. Kobayashi, F. Matsumoto, R. Fukui, T. Kouro, et al. (2007)
J. Exp. Med. 204, 2963-2976
   Abstract »    Full Text »    PDF »
The Lipopolysaccharide Adjuvant Effect on T Cells Relies on Nonoverlapping Contributions from the MyD88 Pathway and CD11c+ Cells.
J. P. McAleer, D. J. Zammit, L. Lefrancois, R. J. Rossi, and A. T. Vella (2007)
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 »

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