We have previously reported the identification, using human immune sera, of 
mimotopes of human hepatitis B virus surface Ag (HBsAg) displayed on filamentous 
phage. To test if these mimotopes could be useful in developing a vaccine 
against the human hepatitis B virus (HBV), we have compared the humoral immune 
response of animals immunized either with a recombinant HBsAg vaccine, or with 
mimotopes. Immunogens were prepared by fusing the mimotopes on different carrier 
molecules (phage coat protein pIII and pVIII, recombinant human H ferritin, HBV 
core peptide) and by synthesizing multiple antigenic peptides carrying the 
mimotopes' amino acid sequences. These immunogens were injected into mice and 
rabbits and sera were collected and tested for the presence of HBsAg-specific 
Abs. Our data confirm that mimotopes can induce a humoral immune response 
resembling that induced by the original Ag, and HBsAg mimotopes displayed on 
phage prove to be the best immunogens, inducing the most reproducible and potent 
immunization. Mimotopes that react as HBV subtype-specific Ags do not show this 
specificity as immunogen and induce a nonsubtype-restricted response. 
Furthermore, mimotopes displayed on phage elicit a strong response to HBsAg in a 
strain of mouse reported to show a low response to it. These results indicate 
that mimotopes identified from random peptide libraries through utilizing human 
immune sera could be important leads for the derivation of new vaccines.