Biofilm Control Strategies in Dental Health - Antibiofilm Agents: From Diagnosis to Treatment and Prevention - page 306

Another approach in designing vaccines against caries has been the use of DNA
vaccines. These vaccines are composed of bacterial plasmids that are delivered to
the host, after which some cells uptake the plasmids and begin producing the
antigen of interest. Expression plasmid DNA contains antigen-encoding sequences
cloned under heterologous promoter control that are delivered by different tech-
niques and lead to antigen expression in transfected cells in vivo (Williams
et al. 2009 ). Several DNA vaccines have been designed for use in caries therapy.
A fusion anti-caries DNA vaccine (pGJA-P/VAX) that encodes two important
antigenic domains (PAc and GLU) of S. mutans was successful in reducing the
levels of dental caries caused by S. mutans in gnotobiotic animals (Niu et al. 2009 ).
Two other vaccines, pGJGAC/VAX and pGJGA-5C/VAX, constructed by cloning
different sections of the catalytic regions of GTFs, protected against cariogenic
bacteria, and specifically against S. sobrinus (Sun et al. 2009 ).
Most immunization approaches, both active and passive, against periodontitis
have been focused on P. gingivalis and A. actinomycetemcomitans . As noted above,
P. gingivalis has been implicated as a major periodontopathogen in human peri-
odontitis. In this context, it has developed a variety of survival strategies enabling it
to evade host defense mechanisms. Virulence factors of P. gingivalis include
cysteine proteases, fimbriae, capsular polysaccharide (CPS), lipopolysaccharide,
and outer membrane vesicles (Holt et al. 1999 ).
There have also been attempts to use inactivated whole cells of P. gingivalis as
antigens in vaccine development. In a recent study, a mixed vaccine of whole
P. gingivalis and F. nucleatum cells suppressed inflammation but failed to prevent
disease progression in an animal model system (Polak et al. 2010 ).
RgpA and Kgp are polyprotein proteinases with C-terminal adhesin domains that
are proteolytically processed. An RgpA-Kgp complex vaccine produced a high
antibody titer in animals which protected them from a P. gingivalis challenge
(O-Brien-Simpson et al. 2003 ; Rajapakse et al. 2002 ). FimA and the 40-kDa
outer membrane protein of P. gingivalis have also been used in designing vaccines
against periodontitis (Lucchese et al. 2013 ; Namikoshi et al. 2003 ).
As in the case of caries vaccines, a new generation of DNA vaccines have also
been devised against FimA (Yu et al. 2011 ) and the 40-kDa outer membrane (Zhang
et al. 2009 )of P. gingivalis, eliciting a protective immune response.
A. actinomycetemcomitans is considered another important pathogen in human
periodontal disease, especially in the localized form of juvenile aggressive peri-
odontitis. Honma et al. demonstrated that high salivary IgA response could be
induced against a fimbrial synthetic peptide by intranasal mucosal immunization
(Honma et al. 1999 ). Harano et al. using olegopeptides from frimbriae, prepared an
antiserum that blocked the adhesion of the organism to saliva-coated hydroxyapa-
tite beads, to buccal epithelial cells, and to a fibroblast cell line (Harano et al. 1995 ).
Also, subcutaneous and intranasal immunization of mice with a capsular serotype
b-specific polysaccharide antigen of A. actinomycetemcomitans resulted in specific
antibodies that efficiently opsonized the organism (Takamatsu-Matsushita
et al. 1996 ). Antibodies elicited against fimbriae composed of a 54 kDa protein
derived from A. actinomycetemcomitans protected against continued infection by