Puumala (PUU) hantavirus strain differences and insertion positions in thehepatitis B virus core antigen influence B-cell immunogenicity and protective potential of core-derived particles

Hepatitis a virus (HBV) core-derived chimeric particles carrying a Puumala (PUU) hantavirus (strain Vranica/Hallnas) nucleocapsid (N) protein sequence (aa 1-45), alternatively inserted at three distinct positions (N-, C-termi nus, or the internal region), and mosaic particles consisting of HBV core a s well as core/PUU (Vranica/Hallnas) N (aa 1-45) readthrough protein were g enerated. Chimeric particles carrying the insert at the N-terminus or the i nternal region of core induced some protective immune response in bank vole s (Clethrionomys glareolus) against a subsequent PUU virus (strain Kazan) c hallenge; 40-50% of the animals showed markers of protection. In contrast, internal insertion of PUU strain CG 18-20 N (aa 1-45) into the HBV core cau sed a highly protective immune response in the bank vole model. Immunizatio ns with particles carrying aa 75-119 of PUU (CG18-20) N at the C-terminus o f 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 votes immunized with chimeric particles containing internal and N-ter minal fusions of PUU N protein but also in animals immunized with the corre sponding mosaic particles. Except for the exclusive occurrence of antibodie s directed against aa 231-240 of N in non-protected animals post virus chal lenge, there was no additional obvious difference in the epitope-specificit y of N-specific antibodies from immunized animals prior and post virus chal lenge, (C) 2000 Academic Press.