Urease-specific monoclonal antibodies prevent Helicobacter felis infection in mice.
Experiments were performed to determine the antigenic specificity of a monoclonal antibody (immunoglobulin A [IgA] 71) previously demonstrated to neutralize the ability of Helicobacter felis to colonize mice. Immunoprecipitation of radiolabeled H. felis outer membrane proteins with IgA 71 revealed specificity for a 62-kDa protein. Another of our monoclonal antibodies, IgG 40, precipitated a protein of similar molecular weight. IgA 71 but not IgG 40 also precipitated purified recombinant H. pylori urease. The antigenic specificity of both antibodies was confirmed to be urease by the ability of each to select Escherichia coli clones expressing the H. felis urease genes. The two antibodies were shown to bind nonoverlapping epitopes in a competition enzyme-linked immunosorbent assay. Both IgA 71 and IgG 40 could effectively neutralize H. felis infectivity by incubating the bacteria with the antibodies prior to oral administration to naive mice. The mechanism of protection does not appear to be inhibition of urease activity, as IgA 71 does not inhibit the conversion of urea to ammonia by H. pylori urease in vitro. These results support a protective role for the secretory humoral immune response in Helicobacter immunity and provide further evidence that the urease enzyme can serve as a protective antigen.
Blanchard
T G
TG
Institute of Pathology, Case Western Reserve University, Cleveland, Ohio 44106.
Czinn
S J
SJ
Maurer
R
R
Thomas
W D
WD
Soman
G
G
Nedrud
J G
JG
D000595:Amino Acid Sequence; D000818:Animals; D000907:Antibodies, Bacterial / Q000627:therapeutic use; D000911:Antibodies, Monoclonal / Q000627:therapeutic use*; D000942:Antigens, Bacterial / Q000235:genetics / Q000276:immunology; D001425:Bacterial Outer Membrane Proteins / Q000276:immunology; D001483:Base Sequence; D017931:DNA Primers / Q000737:chemistry; D018604:Epitope Mapping; D016998:Helicobacter / Q000276:immunology*; D016481:Helicobacter Infections / Q000517:prevention & control*; D007116:Immunization, Passive; D051379:Mice; D008969:Molecular Sequence Data; D014510:Urease / Q000037:antagonists & inhibitors / Q000276:immunology*
D000907:Antibodies, Bacterial; D000911:Antibodies, Monoclonal; D000942:Antigens, Bacterial; D001425:Bacterial Outer Membrane Proteins; D017931:DNA Primers; D014510:Urease