Hepatitis B virus capsid-like particles (CLPs), icosahedral assemblies formed by 90 or 120 core
protein dimers, hold promise as immune-enhancing
vaccine carriers for
heterologous antigens. Insertions into the immunodominant c/e1
B cell epitope, a surface-exposed loop, are especially immunogenic. However, display of whole
proteins, desirable to induce multispecific and possibly
neutralizing antibody responses, can be restrained by an unsuitable structure of the foreign
protein and by its propensity to undergo homomeric interactions. Here we analyzed CLP formation by core fusions with two distinct variants of the dimeric outer surface
lipoprotein C (
OspC) of the
Lyme disease agent Borrelia burgdorferi. Although the topology of the termini in the
OspC dimer does not match that of the insertion sites in the carrier dimer, both fusions, coreOspCa and coreOspCb, efficiently formed stable CLPs. Electron cryomicroscopy clearly revealed the surface disposition of the
OspC domains, possibly with
OspC dimerization occurring across different core
protein dimers. In mice, both CLP preparations induced high-titered antibody responses against the homologous
OspC variant, but with substantial cross-reactivity against the other variant. Importantly, both conferred protection to mice challenged with B. burgdorferi. These data show the principal applicability of hepatitis B virus CLPs for the display of dimeric
proteins, demonstrate the presence in
OspC of hitherto uncharacterized
epitopes, and suggest that
OspC, despite its genetic variability, may be a valid
vaccine candidate.