Monoclonal antibody recognizing pre-S(2) epitope of hepatitis B virus: characterization of pre-S(2) epitope and anti-pre-S(2) antibody.
A hybrid cell line producing monoclonal antibodies recognizing an epitope encoded by the pre-(S)2 region of hepatitis B virus (HBV) genome was obtained by fusion of mouse myeloma cells with lymphocytes from mice immunized with HBV. The monoclonal antibody Mo-F124 secreted from the hybrid line reacted with the pre-S(2) epitope expressed on the surface of both viral and recombinant HBsAg particles--pre-S(2) and S gene product--localised on 34 kD glycoprotein of the viral envelope. The pre-S(2) epitope was sensitive to digestion with V8 protease from Staphylococcus aureus. The enzyme abolished reactivity with Mo-F124 and polymerized human serum albumin (pHSA) binding activity of recombinant particles. Mo-F124 antibody was used to develop highly sensitive radioimmunoassays for determination of pre-S(2) epitope and anti-pre-S(2) antibody in sera of hepatitis B patients. Detection of a pre-S(2) epitope by the monoclonal antibody-based assay in the early phase of acute HBV infection correlated well with the presence of markers of active viral replication (HBeAg, HBV DNA). The appearance of anti-pre-S(2) antibody, usually in the third month after onset of symptoms, was followed by elimination of circulating HBsAg and seroconversion to anti-HBs in all tested cases of uncomplicated acute hepatitis followed by recovery. Anti-pre-S(2) response was not observed in patients with chronic hepatitis B or acute HBV infection progressing to chronic disease. The observed correlation of anti-pre-S(2) response with recovery suggests that the pre-S(2) epitope may represent one of the epitopes inducing antibodies that neutralize the hepatitis B virus.
D000208:Acute Disease; D000818:Animals; D000911:Antibodies, Monoclonal; D002908:Chronic Disease; D000939:Epitopes / Q000032:analysis*; D006514:Hepatitis B Surface Antigens / Q000276:immunology*; D006515:Hepatitis B virus / Q000276:immunology / Q000302:isolation & purification; D006801:Humans; D051379:Mice; D008807:Mice, Inbred BALB C; D011863:Radioimmunoassay; D011994:Recombinant Proteins / Q000032:analysis / Q000276:immunology*
D000911:Antibodies, Monoclonal; D000939:Epitopes; D006514:Hepatitis B Surface Antigens; D011994:Recombinant Proteins