UREASE-SPECIFIC MONOCLONAL-ANTIBODIES PREVENT HELICOBACTER-FELIS INFECTION IN MICE

Experiments were performed to determine the antigenic specificity of a monoclonal antibody (immunoglobulin A [IgG] 71) previously demonstrat ed to neutralize the ability of Helicobacter felis to colonize mice. I mmunoprecipitation of radiolabeled H. felis outer membrane proteins wi th IgA 71 revealed specificity for a 62-kDa protein, Another of our mo noclonal antibodies, IgG 40, precipitated a protein of similar molecul ar weight. IgA 71 but not IgG 40 also precipitated purified recombinan t H. pylori urease, The antigenic specificity of both antibodies was c onfirmed to be urease by the ability of each to select Escherichia coi l 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 neutrali ze H. felis infectivity by incubating the bacteria with the antibodies prior to oral administration to naive mice. The mechanism of protecti on 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 humor al immune response in Helicobacter immunity and provide further eviden ce that the urease enzyme can serve as a protective antigen.