VNPs as Tools for Nanomedicine - Viral Nanoparticles: Tools for Materials Science and Biomedicine - page 213

virus strain is a strain whose pathogenicity has been
reduced. Attenuated virus strains are still infectious; however, their
virulence is reduced to a level where it is no longer dangerous. Attenuated
viruses have historically been generated by serial passage through non-
human hosts or cell lines, and through such passage undergo selection for
genetic modifications that result in reduced virulence in humans. The overall
structural and immunogenic properties of attenuated viruses are usually
not sufficiently altered and provide natural interactions with cells and the
immune system. Some disadvantages of attenuated virus vaccines are when
the viruses cannot be sufficiently attenuated to eliminate adverse affects
while maintaining effective immune priming, as well as potential reversion
to the virulent genotype (Doan

An attenuated

., 2005).
A more recent trend is the development of VLPs as vaccines. VLPs are self-
assembled from coat protein monomers. The monomers can be produced
in heterologous expression systems; a range of systems are available as
discussed in Chapter 3. Purified coat proteins can be self-assembled into
intact nucleic acid-free VLPs. VLPs do not contain viral nucleic acids, and
are thus non-infectious and replication-deficient, making them safer for
use in humans.
A number of VLP-based vaccines have been licensed, or are in clinical and
preclinical trials (reviewed in Garcea & Gissmann, 2004; Grgacic & Anderson,
2006; Ludwig & Wagner, 2007). Commercialized VLP-based vaccines have
been shown to elicit a protective immune response in humans; for example,
VLP-based vaccines using VLPs formed by human papilloma virus (HPV),
polyomavirus, or hepatitis B virus (HBV) coat proteins have been shown to
be protective against the pathogens (reviewed in Garcea & Gissmann, 2004;
Grgacic & Anderson, 2006; Ludwig & Wagner, 2007).
Chimeras

et al

are VLP- or VNP-based assemblies that deliver immunogenic
epitopes of other pathogens (an epitope is an immunogenic peptide or
protein fragment). HBV VLPs and HPV VLPs, for example, have been used
as platforms for the presentation of foreign (= non-HBV- or HPV-derived)
antigenic sequences. The VLP is used as a carrier and serves as an adjuvant
to boost the immune response. Besides utilizing VLPs derived from human
pathogens, a popular strategy exploits the use of plant VNPs and phages as
epitope carriers.
VLPs and VNPs are immunogenic because of their highly ordered and
repetitive structures that are recognized as pathogen-associated molecular
patterns (PAMPs) by the immune system. The quasi-crystalline nature
of the VLP/VNP facilitates pattern recognition by specific and innate
immune responses. The highly immunogenic properties of VLPs and VNPs
are derived from their interaction with and activation of dendritic cells.