STRUCTURAL MIMICRY AND ENHANCED IMMUNOGENICITY OF PEPTIDE EPITOPES DISPLAYED ON FILAMENTOUS BACTERIOPHAGE - THE V3 LOOP OF HIV-1 GP120

The principal neutralizing determinant of the human immunodeficiency v irus type 1 (HIV-1) is an intra-chain disulphide-bridged loop, designa ted V3, in the third hypervariable region of the surface glycoprotein gp 120. Peptide sequences from the V3 loop of gp 120 from HIV-1 strain MN (HIV-1(MX)) were engineered into the N-terminal region of the majo r coat protein of filamentous bacteriophage fd, leading to their displ ay in multiple copies on the surface of the bacteriophage virion. Pept ides displayed in this way were shown to be remarkably effective struc tural mimics of the natural epitope. They were recognised by human HIV antisera and evoked high titres of antibodies in mice, which cross-re acted with other strains of HIV and were capable of neutralizing the v irus. In addition, antibody production could be stimulated by simultan eous inoculation with T-cell epitopes similarly displayed on filamento us bacteriophage. The bacteriophage display system offers a powerful m eans of studying the immunological recognition of proteins and is a pr omising vaccine model.