The Flock House virus (FHV) is an attractive system for bioengineering. The viral particles are stable, and can be produced in large quantities. The viral capsid is readily amenable to protein engineering, offering possible applications in generating vaccines and antitoxins, as well as in tumor targeting, tumor imaging and destruction. The high-resolution X-ray structure of FHV revealed many surface exposed loops on FHV that are amenable to the insertion of peptides or proteins and as well as the potential for the chemical attachment of ligands.
Flock House particles as scaffolds to display anthrax antitoxins
We are using FHV coat protein for the multivalent display of the VWA domain of capillary morphogenesis protein 2, the cellular receptor for anthrax toxin. Sites for the insertion of the VWA domain in the coat protein were selected based on computational analysis of the high-resolution crystal structure of FHV. The chimeric virus-like-particles (VLPs) generated in the baculovirus system were shown to protect cultured cells from toxic effects of protective antigen and lethal factor (anthrax toxin), indicating that the inserted VWA domain is in a biologically functional form. Preliminary experiments show that rats are protected from toxicity in vivo if lethal toxin is co-administered with chimera.
