Format

Send to

Choose Destination
Clin Vaccine Immunol. 2006 Oct;13(10):1079-86. Epub 2006 Aug 23.

Llama single-chain antibody that blocks lipopolysaccharide binding and signaling: prospects for therapeutic applications.

Author information

1
Department of Cellular Architecture and Dynamics, Faculty of Science, Utrecht University, Utrecht, The Netherlands. m.elkhattabi@bio.uu.nl

Abstract

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.

PMID:
16928888
PMCID:
PMC1595319
DOI:
10.1128/CVI.00107-06
[Indexed for MEDLINE]
Free PMC Article

Supplemental Content

Full text links

Icon for HighWire Icon for PubMed Central
Loading ...
Support Center