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

AbstractHepatitis 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