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Hepatitis B virus capsid-like particles can display the complete, dimeric outer surface protein C and stimulate production of protective antibody responses against Borrelia burgdorferi infection.

Abstract
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.
AuthorsClaudia Skamel, Martin Ploss, Bettina Böttcher, Thomas Stehle, Reinhard Wallich, Markus M Simon, Michael Nassal
JournalThe Journal of biological chemistry (J Biol Chem) Vol. 281 Issue 25 Pg. 17474-17481 (Jun 23 2006) ISSN: 0021-9258 [Print] United States
PMID16621801 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
Chemical References
  • Antigens, Bacterial
  • Bacterial Outer Membrane Proteins
  • Bacterial Vaccines
  • Epitopes, B-Lymphocyte
  • Nucleocapsid Proteins
  • OspC protein
  • nucleocapsid protein, Hepatitis virus
Topics
  • Animals
  • Antigens, Bacterial (chemistry)
  • Bacterial Outer Membrane Proteins (chemistry)
  • Bacterial Vaccines (chemistry)
  • Borrelia burgdorferi (pathogenicity)
  • Dimerization
  • Epitopes, B-Lymphocyte (chemistry)
  • Genetic Variation
  • Mice
  • Mice, Inbred BALB C
  • Mice, SCID
  • Models, Molecular
  • Nucleocapsid Proteins (chemistry)
  • Plasmids (metabolism)
  • Protein Conformation
  • Protein Structure, Tertiary

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