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VLPs have also been reported to interact directly with macrophages and
monocytes, further stimulating induction of the immune response (reviewed
in Garcea & Gissmann, 2004; Grgacic & Anderson, 2006; Ludwig & Wagner,
2007).
Chimeric VNPs displaying antigenic peptide epitopes on the exterior
surface have been developed, where the viral capsid is used as a scaffold for
presenting the epitope and also serves as an adjuvant to boost the immune
response (Acosta-Ramirez
et al
., 2008; Cornuz
et al
., 2008; Kaiser
et al
.,
2007; Lacasse
et al
., 2008; Manayani
et al
., 2007; Maurer
et al
., 2005; Raja
et
al
., 2006, 2007). A broad range of plant VNPs have been
developed as platforms for display of immunogenic epitopes. These include
the plant viruses
., 2003; Smith
et al
Cucumber mosaic virus
(CMV), CPMV, RCNMV,
Tomato
bushy stunt virus
(TBSV), PVX, and TMV (reviewed in Canizares
et al
., 2005;
Johnson
et al
., 1997; Porta & Lomonossoff, 1998; Yusibov
et al
., 2006). For
example, CPMV has been used for the display of the
VP2
epitope. Immunized dogs were protected against lethal challenge with
the pathogen (Langeveld
Canine parvovirus
., 2002). Similar data
were obtained in mink immunized with CPMV particles displaying the
Mink enteritis virus
et al
., 2001; Nicholas
et al
VP2 epitope. The animals were protected against viral
challenge (Dalsgaard
., 1997). Heterologous PVX particles displaying
the HIV type 1 ELDKWA epitope caused the production of neutralizing
antibodies in mice (Brennan
et al
., 1999). Some examples of TMV epitope
display used epitopes from murine hepatitis virus or
et al
Foot and mouth disease
virus
(FMDV), and were successful in conferring protection against virulent
challenge in mice or guinea pigs, respectively (Koo
et al
., 1999; Wu
et al
.,
2003).
Phages and the insect virus
(FHV) (see below) have
also been developed as platforms for potential vaccines. A potential vaccine
against nicotine has been recently developed based on the bacteriophage
Q
Flock House virus
b
. This candidate vaccine is envisioned as a promising strategy for
smoking cessation. By inducing neutralizing antibodies against the addictive
compound nicotine, and reducing blood nicotine levels thereby limiting
transport across the blood-brain barrier, a nicotine vaccine is expected to
reduce cigarette addiction. Q
b
particles covalently modified with nicotine
are currently under investigation in clinical trials (Cornuz
et al
., 2008;
Maurer
., 2005).
Recombinant FHV particles have been developed that have the potential
to function as an anthrax antitoxin and vaccine. Anthrax is an acute and
highly lethal disease caused by the bacterium
et al
. Based
on the potential use of anthrax as a weapon of bioterrorism, there is need
for the development of improved antitoxins and vaccines. Morbidity and
mortality from anthrax are caused mainly by the action of anthrax toxin,
Bacillus anthracis
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