This Article
Right arrow Full Text
Right arrow Full Text (PDF)
Right arrow Alert me when this article is cited
Right arrow Alert me if a correction is posted
Right arrow Citation Map
Services
Right arrow E-mail this article to a friend
Right arrow Similar articles in this journal
Right arrow Similar articles in PubMed
Right arrow Alert me to new issues of the journal
Right arrow Download to citation manager
Right arrowReprints and Permissions
Right arrow Copyright Information
Right arrow Books from ASM Press
Right arrow MicrobeWorld
Citing Articles
Right arrow Citing Articles via Google Scholar
Google Scholar
Right arrow Articles by Morefield, G. L.
Right arrow Articles by Ulrich, R. G.
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Right arrow Articles by Morefield, G. L.
Right arrow Articles by Ulrich, R. G.

 Previous Article  |  Next Article 

Clinical and Vaccine Immunology, November 2007, p. 1499-1504, Vol. 14, No. 11
1071-412X/07/$08.00+0     doi:10.1128/CVI.00153-07
Copyright © 2007, American Society for Microbiology. All Rights Reserved.

Synthetic Toll-Like Receptor 4 Agonist Enhances Vaccine Efficacy in an Experimental Model of Toxic Shock Syndrome{triangledown}

Garry L. Morefield,1 Lynn D. Hawkins,2 Sally T. Ishizaka,2 Teri L. Kissner,1 and Robert G. Ulrich1*

Laboratory of Molecular Immunology, U.S. Army Medical Research Institute of Infectious Diseases, Frederick, Maryland 21702,1 Eisai Research Institute, Andover, Massachusetts 018872

Received 24 March 2007/ Returned for modification 14 June 2007/ Accepted 5 August 2007

The development of new protein subunit vaccines has stimulated the search for improved adjuvants to replace traditional aluminum-containing products. We investigated the adjuvant effects of a synthetic Toll-like receptor 4 (TLR4) agonist on vaccine efficacy in an experimental model of toxic shock syndrome. The TLR4 agonist E6020 has a simplified structure consisting of a hexa-acylated acyclic backbone. The vaccine examined is a recombinantly attenuated form of staphylococcal enterotoxin B (STEBVax). Using cells stably transfected with TLRs, E6020 transduced signals only through TLR4, suggesting monospecificity, while Escherichia coli 055:B5 lipopolysaccharide activated both the TLR2/6 heterodimer and TLR4. Coadministration of E6020 with STEBVax, by the intramuscular or intranasal route, induced significant levels of immunoglobulin G (IgG) in BALB/c mice. Further, increased IgG production resulted from the combination of E6020 with aluminum hydroxide adjuvant (AH). The antibody response to the vaccine coadministered with E6020 was a mixed Th1/Th2 response, as opposed to the Th2-biased response obtained with AH. Mice vaccinated with STEBVax coadministered with AH, TLR4 agonists, or a combination of both adjuvants were protected from toxic shock. Our data demonstrate the effectiveness of the synthetic TLR4 agonist E6020 as an alternative adjuvant for protein subunit vaccines that may also be used in combination with traditional aluminum-containing adjuvants.

* Corresponding author. Mailing address: Laboratory of Molecular Immunology, U.S. Army Medical Research Institute of Infectious Diseases, Frederick, MD 21702. Phone: (301) 619-4232. Fax: (301) 619-2348. E-mail: ulrich{at}ncifcrf.gov

{triangledown} Published ahead of print on 22 August 2007.

Clinical and Vaccine Immunology, November 2007, p. 1499-1504, Vol. 14, No. 11
1071-412X/07/$08.00+0     doi:10.1128/CVI.00153-07
Copyright © 2007, American Society for Microbiology. All Rights Reserved.





Copyright © 2010 by the American Society for Microbiology.   For an alternate route to Journals.ASM.org, visit: http://intl-journals.asm.org | More Info»