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
Services
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 HighWire
Right arrow Citing Articles via Google Scholar
Google Scholar
Right arrow Articles by El Khattabi, M.
Right arrow Articles by Stam, J.
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Right arrow Articles by El Khattabi, M.
Right arrow Articles by Stam, J.

 Previous Article  |  Next Article 

Clinical and Vaccine Immunology, October 2006, p. 1079-1086, Vol. 13, No. 10
1071-412X/06/$08.00+0     doi:10.1128/CVI.00107-06
Copyright © 2006, American Society for Microbiology. All Rights Reserved.

Llama Single-Chain Antibody That Blocks Lipopolysaccharide Binding and Signaling: Prospects for Therapeutic Applications{triangledown}

Mohamed El Khattabi,1* Hendrik Adams,1 Erik Heezius,2 Pim Hermans,3 Frank Detmers,3 Bram Maassen,1 Peter van der Ley,4 Jan Tommassen,5 Theo Verrips,1 and Jord Stam1

Department of Cellular Architecture and Dynamics, Faculty of Science, Utrecht University, Utrecht,1 Eijkman-Winkler Institute for Medical Microbiology, University Medical Center, Utrecht,2 BAC BV, Naarden,3 Netherlands Vaccine Institute, De Bilt,4 Department of Molecular Microbiology, Faculty of Science, Utrecht University, Utrecht, The Netherlands5

Received 27 February 2006/ Returned for modification 16 May 2006/ Accepted 11 August 2006

Sepsis is a considerable health problem and a burden on the health care system. Endotoxin, or lipopolysaccharide (LPS), present in the outer membrane of gram-negative bacteria, is responsible for more than 50% of the sepsis cases and is, therefore, a legitimate target for therapeutic approaches against sepsis. In this study, we selected and characterized a llama single-chain antibody fragment (VHH) directed to Neisseria meningitidis LPS. The VHH, designated VHH 5G, showed affinity to purified LPS as well as to LPS on the surfaces of the bacteria. Epitope mapping using a panel of N. meningitidis mutants revealed that VHH 5G recognizes an epitope in the inner core of LPS, and as expected, the VHH proved to have broad specificity for LPS from different bacteria. Furthermore, this VHH blocked binding of LPS to target cells of the immune system, resulting in the inhibition of LPS signaling in whole blood. Moreover, it was found to remove LPS efficiently from aqueous solutions, including serum. The selected anti-LPS VHH is a leading candidate for therapies against LPS-mediated sepsis.

* Corresponding author. Mailing address: Padualaan 8, 3584 CH Utrecht, The Netherlands. Phone: 31-30-2533350. Fax: 31-30-2513655. E-mail: m.elkhattabi{at}bio.uu.nl.

{triangledown} Published ahead of print on 23 August 2006.

Clinical and Vaccine Immunology, October 2006, p. 1079-1086, Vol. 13, No. 10
1071-412X/06/$08.00+0     doi:10.1128/CVI.00107-06
Copyright © 2006, American Society for Microbiology. All Rights Reserved.



This article has been cited by other articles:

  • Monegal, A., Ami, D., Martinelli, C., Huang, H., Aliprandi, M., Capasso, P., Francavilla, C., Ossolengo, G., de Marco, A. (2009). Immunological applications of single-domain llama recombinant antibodies isolated from a naive library. Protein Eng Des Sel 22: 273-280 [Abstract] [Full Text]  


Copyright © 2009 by the American Society for Microbiology.   For an alternate route to Journals.ASM.org, visit: http://intl-journals.asm.org | More Info»