VNPs as Tools for Nanomedicine - Viral Nanoparticles: Tools for Materials Science and Biomedicine - page 215

which consists of a cell binding protein, protective antigen (PA), and two
enzymatic components, edema factor and lethal factor. During infection
the toxin components are produced by

and PA binds to anthrax
toxin receptors, which are widely distributed on human cells, and leads to
internalization of the toxin (Mock & Fouet, 2001; Mock & Mignot, 2003). FHV
particles were genetically engineered to express and display the anthrax
receptor on the surface of the viral capsid (Fig. 8.3a) (Manayani

B. anthracis

.,
2007). These anthrax receptor-displaying FHV particles efficiently bind to
PA. Studies in a rat animal model showed that this strategy inhibited lethal
toxin action (Manayani

et al

., 2007). Furthermore, it was demonstrated that
FHV-receptor chimeras further complexed with PA produced a multivalent
array of PA antigen (Fig. 8.3b). This complex was more immunogenic than
monomeric PA, and successfully elicited the production of antibodies
that protected rats from anthrax lethal toxin challenge after a single dose
(Manayani

et al

., 2007).
In summary, a variety of VNPs have been utilized as platforms for
the development of novel vaccines. The highly ordered protein scaffold
in combination with the ease of manipulation (genetic or chemical
engineering) makes VNPs attractive candidates for such development.

et al

Figure 8.3 3-D models of FHV-VWAANTXR2 VLPs (anthrax-receptor-displaying Flock

House virus particles) alone (a) or with bound PA83 (PA = protective antigen) (b).

Pseudoatomic models of the FHV-VWAANTXR2 chimera. X-ray coordinates of FHV
capsid protein (green) and ANTXR2 VWA domain (yellow) were docked into the
cryo-electron microscopic density. Surface views of the particles in the absence of
the cryoEM density maps. (b) model of PA83 bound to the surface of FHV-

VWAANTXR2 chimeras. PA83 (purple) was modeled onto the surface of the FHV-
VWAANTXR2 VLP using the known high-resolution X-ray structure of the ANTXR2-
VWA/PA63 complex as a guide. Reproduced Manayani, D. J., Thomas, D., Dryden, K. A.,
Reddy, V., Siladi, M. E., Marlett, J. M., Rainey, G. J., Pique, M. E., Scobie, H. M., Yeager, M.,
Young, J. A., Manchester, M., and Schneemann, A. (2007) A viral nanoparticle with dual
function as an anthrax antitoxin and vaccine,

In silico

PLoS Pathog. , 3 (10), 1422-1431.