Interactions between hepatitis B virus and polymeric human serum albumin. II. Development of syngeneic monoclonal anti-anti-idiotypes which mimic hepatitis B surface antigen in the induction of immune responsiveness.

We used monoclonal anti-idiotypes (anti-Id) 63.14, previously shown to mimic polymeric human serum albumin (polyHSA) and bind its receptor on hepatitis B surface antigen (HBsAg), to produce syngeneic monoclonal anti-anti-Id (Ab3) which could bear the internal image of HBsAg and mimic its immunogenicity in vivo. Nine hybridomas obtained from spleen cells of BALB/c mice immunized with 63.14 were isolated, which were able to inhibit the binding of alkaline phosphatase-conjugated 63.14 to HBsAg. Both direct and competition enzyme-linked immunosorbent assay (ELISA) showed that 4 of these clones were able to mimic HBsAg since they reacted with polyHSA and inhibited the binding of monoclonal and polyclonal anti-HBsAg to the viral antigen. To determine whether these Ab3 could induce an immune response against HBsAg in vivo, we injected a series of rabbits with Ab3 G11 or HBsAg and tested their sera after the second boost. ELISA, radioimmunoassay and Western blot experiments showed that G11 was as effective as HBsAg in inducing a specific anti-HBsAg immune response. These data indicate that our Ab3 can mimic HBsAg both in vitro and in vivo and might be useful as alternative vaccine for HBV infection.