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Adjuvant-Enhanced Antibody Responses in the Absence of Toll-Like Receptor Signaling
Amanda L. Gavin,1Kasper Hoebe,1Bao Duong,1,2Takayuki Ota,1Christopher Martin,1,2Bruce Beutler,1David Nemazee1*
Innate immune signals mediated by Toll-like receptors (TLRs)have been thought to contribute considerably to the antibody-enhancingeffects of vaccine adjuvants. However, we report here that micedeficient in the critical signaling components for TLR mountrobust antibody responses to T cell–dependent antigengiven in four typical adjuvants: alum, Freund's complete adjuvant,Freund's incomplete adjuvant, and monophosphoryl-lipid A/trehalosedicorynomycolate adjuvant. We conclude that TLR signaling doesnot account for the action of classical adjuvants and does notfully explain the action of a strong adjuvant containing a TLRligand. This may have important implications in the use anddevelopment 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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