A molecular assembly system for presentation of antigens on the surface of HBc virus-like particles

Hepatitis B virus-like particles, icosahedral structures formed by multiple core protein dimers, are promising immune-enhancing vaccine carriers for foreign antigens. Insertions into the surface-exposed immunodominant loop are especially immunogenic. However, the need to conserve the particulate structure to ensure high immunogenicity imposes restraints on the nature of the heterologous sequence that can be inserted. We propose a new approach to constructing HBc particles linked to the target epitopes that relies on non-covalent interactions between the epitope and pre-assembled unmodified HBc particles. Interaction was enabled by fusion of the epitope to the GSLLGRMKGA peptide, binding to the spike tips. This peptide may be used as a “binding tag” allowing in vitro construction of HBc particles carrying the target peptide. Such virus-like particles carrying multiple copies of the extracellular domain of the M2 protein of different influenza strains appeared to be highly immunogenic and protected immunised mice against a lethal influenza challenge.

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► Recombinant HBc particles are widely used to display immunodominant epitopes.
► Insertion of epitopes into the HBc protein frequently affects the formation of particles.
► Target peptides may be non-covalently bound to pre-assembled HBc particles in vitro.
► HBc particles coated with multiple copies of the M2e peptide of the influenza virus were produced.
► M2eHBc complexes are highly immunogenic and protect mice against influenza challenge.