Core particles of hepatitis B virus as carrier for foreign epitopes.
To be effective as vaccines, most monomeric proteins and peptides either require chemical coupling to high molecular weight carriers or application together with adjuvants. More recently, recombinant DNA techniques have been used to insert foreign epitopes into proteins with inherent multimerization capacity, such as particle-forming viral capsid or envelope proteins. The core protein of hepatitis B virus (HBcAg), because of its unique structural and immunological properties, has gained widespread interest as a potential antigen carrier. Foreign sequences of up to approximately 40 amino acid residues at the N terminus, 50 or 100 amino acids in the central immunodominant c/e 1 epitope region of HBcAg, and up to 100 or even more residues at the C terminus, did not interfere with particle formation. The humoral immunogenicity of inserted epitopes is determined by the immunogenicity of the peptide itself and its surface exposure, and is influenced by the route of application. The probably flexible and surface-exposed c/e1 region emerged as the most promising insertion site. When applied together with adjuvants approved for human and veterinary use, or even without adjuvants, such chimeric particles induced B and T cell immune responses against the inserted epitopes. In some cases neutralizing antibodies, cytotoxic T cells and protection against challenge with the intact pathogen were demonstrated. Major factors for the potentiated immune response against the foreign epitopes are the multimeric structure of chimeric HBcAg that results in a high epitope density per particle, and the provision of T cell help by the carrier moiety. Beyond its use as subunit vaccine, chimeric HBcAg produced in attenuated Salmonella strains may be applicable as live vaccine.
Ulrich
R
R
Charité Medical School, Humboldt University, Berlin, Germany.
Nassal
M
M
Meisel
H
H
Krüger
D H
DH
D000939:Epitopes / Q000737:chemistry / Q000235:genetics / Q000276:immunology*; D015967:Gene Expression Regulation, Viral / Q000276:immunology; D006512:Hepatitis B Core Antigens / Q000737:chemistry / Q000276:immunology / Q000502:physiology*; D006515:Hepatitis B virus / Q000737:chemistry / Q000502:physiology*; D006801:Humans; D008854:Microscopy, Electron; D011993:Recombinant Fusion Proteins / Q000138:chemical synthesis* / Q000276:immunology*; D014765:Viral Vaccines / Q000138:chemical synthesis*
D000939:Epitopes; D006512:Hepatitis B Core Antigens; D011993:Recombinant Fusion Proteins; D014765:Viral Vaccines