title: Puumala (PUU) hantavirus strain differences and insertion positions in the hepatitis B virus core antigen influence B-cell immunogenicity and protective potential of core-derived particles.
abstract: Hepatitis B virus (HBV) core-derived chimeric particles carrying a Puumala (PUU) hantavirus (strain Vranica/Hällnäs) nucleocapsid (N) protein sequence (aa 1-45), alternatively inserted at three distinct positions (N-, C-terminus, or the internal region), and mosaic particles consisting of HBV core as well as core/PUU (Vranica/Hällnäs) N (aa 1-45) readthrough protein were generated. Chimeric particles carrying the insert at the N-terminus or the internal region of core induced some protective immune response in bank voles (Clethrionomys glareolus) against a subsequent PUU virus (strain Kazan) challenge; 40-50% of the animals showed markers of protection. In contrast, internal insertion of PUU strain CG18-20 N (aa 1-45) into the HBV core caused a highly protective immune response in the bank vole model. Immunizations with particles carrying aa 75-119 of PUU (CG18-20) N at the C-terminus of core verified the presence of a second, minor protective region in the N protein. A strong PUU N-specific antibody response was detected not only in bank voles immunized with chimeric particles containing internal and N-terminal fusions of PUU N protein but also in animals immunized with the corresponding mosaic particles. Except for the exclusive occurrence of antibodies directed against aa 231-240 of N in non-protected animals post virus challenge, there was no additional obvious difference in the epitope-specificity of N-specific antibodies from immunized animals prior and post virus challenge.
authors.affiliation: Microbiology and Tumor Biology Center, Karolinska Institutet, Stockholm, Sweden.
authors.forename: D
authors.initials: D
authors.lastname: Koletzki
authors.forename: A
authors.initials: A
authors.lastname: Lundkvist
authors.forename: K B
authors.initials: KB
authors.lastname: Sjölander
authors.forename: H R
authors.initials: HR
authors.lastname: Gelderblom
authors.forename: M
authors.initials: M
authors.lastname: Niedrig
authors.forename: H
authors.initials: H
authors.lastname: Meisel
authors.forename: D H
authors.initials: DH
authors.lastname: Krüger
authors.forename: R
authors.initials: R
authors.lastname: Ulrich
mesh_terms: D000595:Amino Acid Sequence; D000818:Animals; D000914:Antibodies, Viral / Q000276:immunology; D003411:Arvicolinae; D001402:B-Lymphocytes / Q000276:immunology*; D018985:Epitopes, B-Lymphocyte / Q000276:immunology; D004926:Escherichia coli; D006476:Orthohantavirus / Q000145:classification / Q000276:immunology*; D018778:Hantavirus Infections / Q000276:immunology / Q000517:prevention & control*; D006512:Hepatitis B Core Antigens / Q000276:immunology*; D006515:Hepatitis B virus / Q000276:immunology*; D008969:Molecular Sequence Data; D019251:Nucleocapsid / Q000276:immunology*; D019590:Nucleocapsid Proteins; D013045:Species Specificity; D014614:Vaccines, Synthetic / Q000737:chemistry / Q000235:genetics / Q000276:immunology
chemical_list: D000914:Antibodies, Viral; D018985:Epitopes, B-Lymphocyte; D006512:Hepatitis B Core Antigens; D019590:Nucleocapsid Proteins; D014614:Vaccines, Synthetic; C100886:nucleocapsid protein, Puumala virus