Llama single-chain antibody that blocks lipopolysaccharide binding and signaling: prospects for therapeutic applications.
Clin Vaccine Immunol
; 13(10): 1079-86, 2006 Oct.
Article
em En
| MEDLINE
| ID: mdl-16928888
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.
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Fragmentos Fab das Imunoglobulinas
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Camelídeos Americanos
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Transdução de Sinais
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Lipopolissacarídeos
Limite:
Animals
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Humans
Idioma:
En
Ano de publicação:
2006
Tipo de documento:
Article