DERIVATION OF VACCINES FROM MIMOTOPES - IMMUNOLOGICAL PROPERTIES OF HUMAN HEPATITIS-B VIRUS SURFACE-ANTIGEN MIMOTOPES DISPLAYED ON FILAMENTOUS PHAGE

We have previously reported the identification, using human immune ser a, of mimotopes of human hepatitis B virus surface Ag (HBsAg) displaye d on filamentous phage. To test if these mimotopes could be useful in developing a vaccine against the human hepatitis B virus (HBV), we hav e compared the humoral immune response of animals immunized either wit h a recombinant HBsAg vaccine, or with mimotopes. Immunogens were prep ared by fusing the mimotopes on different carrier molecules (phage coa t protein pill and pVIII, recombinant human H ferritin, HBV core pepti de) and by synthesizing multiple antigenic peptides carrying the mimot opes' amino acid sequences. These immunogens were injected into mice a nd rabbits and sera were collected and tested for the presence of HBsA g-specific Abs. Our data confirm that mimotopes can induce a humoral i mmune response resembling that induced by the original Ag, and HBsAg m imotopes 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 an d induce a nonsubtype-restricted response. Furthermore, mimotopes disp layed 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 mim otopes identified from random peptide libraries through utilizing huma n immune sera could be important leads for the derivation of new vacci nes.