A human domain antibody and Lewis b glycoconjugate that inhibit binding of Helicobacter pylori to Lewis b receptor and adhesion to human gastric epithelium.
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.
Younson
Justine
J
King's College London, Oral Immunology, Dental Institute, University College London, London, UK.
O'Mahony
Rachel
R
Liu
Haiqun
H
Basset
Christelle
C
Grant
Steven
S
Campion
Colin
C
Jennings
Lisa
L
Vaira
Dino
D
Kelly
Charles G
CG
Roitt
Ivan M
IM
Holton
John
J
D018829:Adhesins, Bacterial / Q000276:immunology*; D000918:Antibody Specificity; D005753:Gastric Mucosa / Q000276:immunology / Q000382:microbiology; D016481:Helicobacter Infections / Q000276:immunology*; D016480:Helicobacter pylori / Q000276:immunology*; D006801:Humans; D007116:Immunization, Passive; D007135:Immunoglobulin Variable Region / Q000276:immunology*; D066298:In Vitro Techniques; D007983:Lewis Blood Group Antigens / Q000276:immunology*; D013270:Stomach / Q000276:immunology / Q000382:microbiology
D018829:Adhesins, Bacterial; C400429:BabA protein, Helicobacter pylori; D007135:Immunoglobulin Variable Region; D007983:Lewis Blood Group Antigens