Behavior of a short preS1 epitope on the surface of hepatitis B core particles

The major immunodominant region of hepatitis B core particles is widely rec ognized as the most prospective target for the insertion of foreign epitope s, ensuring their maximal antigenicity and immunogenicity. This region was mapped around amino acid residues 79-81, which were shown by electron cryo- microscopy to be located on the tips of the spikes protruding from the surf ace of hepatitis B core shells. Here we tried to expose a model sequence, t he short immunodominant hepatitis B preS1 epitope 31-DPAFR-35, onto the tip of the spike, with simultaneous deletion of varying stretches from the maj or immunodominant region of the HBc molecule. Accessibility to the monoclon al anti-preS1 antibody MA18/7 and specific immunogenicity of the preS1 epit ope depended on the location and length of the deletion. While chimeras wit h deletions within the stretch 79-88 presented the preS1 epitope on their s urface and demonstrated remarkable preS1 immunogenicity, the corresponding chimeras without any deletion or with a more prolonged deletion (79-93) wer e unable to provide such presentation and possessed a lower specific preS1 immunogenicity. Deletion of the stretch 79-81 was sufficient to avoid the i ntrinsic HBc immunogenicity of the core particles, although chimeras with d eleted major immunodominant region retained their property to be recognized by human polyclonal or hyperimmune anti-HBc antibodies.