Hepatitis B virus capsid-like particles stimulate protective antibody responses
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According to recently published research from Germany, hepatitis B virus (HBV) capsid-like particles (CLPs) can display the complete, dimeric outer surface protein C and stimulate production of protective antibody responses against Borrelia burgdorferi infection.
“HBV 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/e1B 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,” wrote C. Skamel and colleagues, University of Freiburg Hospital.
“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 B. 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, coreOspC(a) and coreOspC(b), 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,” the authors reported.
“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,” the scientists observed.
They concluded, “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.”
Skamel and colleagues published their study in the Journal of Biological Chemistry (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. J Biol Chem, 2006;281(25):17474-17481).
For more information, contact M. Nassal, University of Freiburg Hospital, Institute of Immunology, Hugstetter Str 55, D-79106 Freiburg, Germany.
Publisher contact information for the Journal of Biological Chemistry is: American Society of Biochemistry & Molecular Biology Inc., 9650 Rockville Pike, Bethesda, MD 20814-3996, USA.
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