Pathogenic, antigenic and molecular properties of rabbit haemorrhagic disease virus (RHDV) isolated from vaccinated rabbits: detection and characterization of antigenic variants

Rabbit haemorrhagic disease virus (RHDV) isolates were obtained from severa l animals previously vaccinated with an inactivated vaccine. Seven isolates were analyzed by immunological and molecular biological methods and compar ed to reference strains. Antigenic characterization with monoclonal antibod ies as well as haemagglutination assays demonstrated considerable differenc es between individual isolates. However, sequencing of the capsid protein g enes revealed a high degree of homology between five of these isolates and the reference strain FRG. In contrast, two isolates specified remarkably di fferent capsid proteins with a degree of variation not observed so far in R HDV. Amino acid alterations were found clustered between residues 301 and 3 28 (region C), 344 and 434 (region E) and also in the 3' region of the caps id protein gene. Interestingly, experimental vaccination of rabbits followe d by challenge with the heterologous variant strains showed restricted cros s-protection against one of the strains. In summary, we found a level of an tigenic variation not detected in RHDV so far, and describe two distinct ne w antigenic variants.