A Human Domain Antibody and Lewis(b) Glycoconjugate That Inhibit Binding of Helicobacter pylori to Lewis(b) Receptor and Adhesion to Human Gastric Epithelium

Justine Younson; Rachel O'Mahony; Haiqun Liu; Steven Grant; Colin Campion; Lisa Jennings; Dino Vaira; Charles G. Kelly; Ivan M. Roitt; John Holton

doi:10.1086/644596

A Human Domain Antibody and Lewis(b) Glycoconjugate That Inhibit Binding of Helicobacter pylori to Lewis(b) Receptor and Adhesion to Human Gastric Epithelium

Justine Younson, Rachel O'Mahony, Haiqun Liu, Steven Grant, Colin Campion, Lisa Jennings, Dino Vaira, Charles G. Kelly, Ivan M. Roitt, John Holton

Centre for Host Microbiome Interactions

Research output: Contribution to journal › Article › peer-review

12 Citations (Scopus)

Abstract

Increasing antibiotic resistance has prompted development of alternative approaches to antimicrobial therapy, including blocking microbial adhesion to host receptors. The BabA adhesin of Helicobacter pylori binds to fucosylated blood group antigens, such as the Lewis(b) antigens in human primate gastric mucosa. We have isolated a human domain antibody specific for BabA that inhibits binding of BabA to Lewis(b) and prevents adhesion of H. pylori to human gastric epithelium. In addition, Lewis(b) oligosaccharides covalently linked to poly-D-lysine inhibited BabA binding to Le(b). The poly-D-lysine-Le(b) hexasaccharide and an Le(b) human serum albumin conjugate not only inhibited adherence of H. pylori to gastric epithelium but also displaced adherent bacteria when added to human stomach sections. Combinations of Le(b) and sialyl Le(x) or domain antibody 25 and sialyl Le(x) acted synergistically. Domain antibody 25 inhibitor may have potential for prophylactic use and, in combination with Le(b) glycoconjugates, therapeutic use in treatment of drug-resistant H. pylori infection.

Original language	English
Pages (from-to)	1574 - 1582
Number of pages	9
Journal	Journal of Infectious Diseases
Volume	200
Issue number	10
DOIs	https://doi.org/10.1086/644596
Publication status	Published - Nov 2009

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Younson, J., O'Mahony, R., Liu, H., Grant, S., Campion, C., Jennings, L., Vaira, D., Kelly, C. G., Roitt, I. M., & Holton, J. (2009). A Human Domain Antibody and Lewis(b) Glycoconjugate That Inhibit Binding of Helicobacter pylori to Lewis(b) Receptor and Adhesion to Human Gastric Epithelium. Journal of Infectious Diseases, 200(10), 1574 - 1582. https://doi.org/10.1086/644596

@article{7311c5eef3d347219d223cdec48ceeb3,

title = "A Human Domain Antibody and Lewis(b) Glycoconjugate That Inhibit Binding of Helicobacter pylori to Lewis(b) Receptor and Adhesion to Human Gastric Epithelium",

abstract = "Increasing antibiotic resistance has prompted development of alternative approaches to antimicrobial therapy, including blocking microbial adhesion to host receptors. The BabA adhesin of Helicobacter pylori binds to fucosylated blood group antigens, such as the Lewis(b) antigens in human primate gastric mucosa. We have isolated a human domain antibody specific for BabA that inhibits binding of BabA to Lewis(b) and prevents adhesion of H. pylori to human gastric epithelium. In addition, Lewis(b) oligosaccharides covalently linked to poly-D-lysine inhibited BabA binding to Le(b). The poly-D-lysine-Le(b) hexasaccharide and an Le(b) human serum albumin conjugate not only inhibited adherence of H. pylori to gastric epithelium but also displaced adherent bacteria when added to human stomach sections. Combinations of Le(b) and sialyl Le(x) or domain antibody 25 and sialyl Le(x) acted synergistically. Domain antibody 25 inhibitor may have potential for prophylactic use and, in combination with Le(b) glycoconjugates, therapeutic use in treatment of drug-resistant H. pylori infection.",

author = "Justine Younson and Rachel O'Mahony and Haiqun Liu and Steven Grant and Colin Campion and Lisa Jennings and Dino Vaira and Kelly, {Charles G.} and Roitt, {Ivan M.} and John Holton",

year = "2009",

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doi = "10.1086/644596",

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Younson, J, O'Mahony, R, Liu, H, Grant, S, Campion, C, Jennings, L, Vaira, D, Kelly, CG, Roitt, IM & Holton, J 2009, 'A Human Domain Antibody and Lewis(b) Glycoconjugate That Inhibit Binding of Helicobacter pylori to Lewis(b) Receptor and Adhesion to Human Gastric Epithelium', Journal of Infectious Diseases, vol. 200, no. 10, pp. 1574 - 1582. https://doi.org/10.1086/644596

TY - JOUR

T1 - A Human Domain Antibody and Lewis(b) Glycoconjugate That Inhibit Binding of Helicobacter pylori to Lewis(b) Receptor and Adhesion to Human Gastric Epithelium

AU - Younson, Justine

AU - O'Mahony, Rachel

AU - Liu, Haiqun

AU - Grant, Steven

AU - Campion, Colin

AU - Jennings, Lisa

AU - Vaira, Dino

AU - Kelly, Charles G.

AU - Roitt, Ivan M.

AU - Holton, John

PY - 2009/11

Y1 - 2009/11

N2 - Increasing antibiotic resistance has prompted development of alternative approaches to antimicrobial therapy, including blocking microbial adhesion to host receptors. The BabA adhesin of Helicobacter pylori binds to fucosylated blood group antigens, such as the Lewis(b) antigens in human primate gastric mucosa. We have isolated a human domain antibody specific for BabA that inhibits binding of BabA to Lewis(b) and prevents adhesion of H. pylori to human gastric epithelium. In addition, Lewis(b) oligosaccharides covalently linked to poly-D-lysine inhibited BabA binding to Le(b). The poly-D-lysine-Le(b) hexasaccharide and an Le(b) human serum albumin conjugate not only inhibited adherence of H. pylori to gastric epithelium but also displaced adherent bacteria when added to human stomach sections. Combinations of Le(b) and sialyl Le(x) or domain antibody 25 and sialyl Le(x) acted synergistically. Domain antibody 25 inhibitor may have potential for prophylactic use and, in combination with Le(b) glycoconjugates, therapeutic use in treatment of drug-resistant H. pylori infection.

AB - Increasing antibiotic resistance has prompted development of alternative approaches to antimicrobial therapy, including blocking microbial adhesion to host receptors. The BabA adhesin of Helicobacter pylori binds to fucosylated blood group antigens, such as the Lewis(b) antigens in human primate gastric mucosa. We have isolated a human domain antibody specific for BabA that inhibits binding of BabA to Lewis(b) and prevents adhesion of H. pylori to human gastric epithelium. In addition, Lewis(b) oligosaccharides covalently linked to poly-D-lysine inhibited BabA binding to Le(b). The poly-D-lysine-Le(b) hexasaccharide and an Le(b) human serum albumin conjugate not only inhibited adherence of H. pylori to gastric epithelium but also displaced adherent bacteria when added to human stomach sections. Combinations of Le(b) and sialyl Le(x) or domain antibody 25 and sialyl Le(x) acted synergistically. Domain antibody 25 inhibitor may have potential for prophylactic use and, in combination with Le(b) glycoconjugates, therapeutic use in treatment of drug-resistant H. pylori infection.

U2 - 10.1086/644596

DO - 10.1086/644596

M3 - Article

VL - 200

SP - 1574

EP - 1582

JO - Journal of Infectious Diseases

JF - Journal of Infectious Diseases

IS - 10

ER -

A Human Domain Antibody and Lewis(b) Glycoconjugate That Inhibit Binding of Helicobacter pylori to Lewis(b) Receptor and Adhesion to Human Gastric Epithelium

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