immune system; and (iv) they can be derivatized (Chap. 4, § 4.4). APols can therefore carry adjuvants
along with the proteins used as immunogen and/or tags that will direct them toward specific cells or
associate them with particles used as carrier, so as to improve the uptake of target MPs. APol particles
resemble, to an extent, the polymeric micelles already used in some vaccine formulations (Trimaille
and Verrier 2015), some of which are based on hydrophobized poly(γ-glutamic acid), a category of
polymers which, as we have seen in Chap. 5 (Table 5.1), can be used as APols (Han et al. 2014). This
intriguing set of potential advantages prompted attempts at using APols in the formulation of vaccines
directed against a widely distributed pathogenic bacterium, C. trachomatis.
Chlamydiae are Gram-negative (Gram
À ) eubacteria, obligate intracellular pathogens, and
symbionts of diverse organisms, ranging from humans to amoebae (reviewed in Bachmann et al.
2014; Elwell et al. 2016). The best-studied group in the Chlamydiae phylum is the Chlamydiaceae
family, which comprises 11 species that are pathogenic to humans or animals. C. trachomatis and
C. pneumoniae, the major species that infect humans, are responsible for a wide range of diseases
(Schachter and Dawson 1978; Centers for Disease Control and Prevention 1999; Schachter 1999).
C. trachomatis is one of the most common human pathogens and is found in all regions of the world,
where it is the leading cause of sexually transmitted bacterial infections. It can produce ocular,
gastrointestinal, and respiratory infections, which can affect persons of all ages. In young individuals,
C. trachomatis is the most common sexually transmitted bacterial pathogen. Genital infections can
remain asymptomatic, but others can produce acute symptomatology. In women, long-term sequelae
such as infertility and ectopic pregnancy can develop. At birth, newborns can become infected in the
eyes and lungs if the mother has a genital tract infection at the time of delivery. In countries with poor
hygienic conditions, young children can have multiple ocular infections that result in the development
of trachoma later in life. C. trachomatis has also been isolated from the lungs of adults, in particular
from immunocompromised patients. Infection with C. trachomatis facilitates the transmission of HIV
and is associated with cervical cancer. C. pneumoniae causes respiratory infections, accounting for
~10% of community-acquired pneumonia, and is linked to a number of chronic diseases, including
asthma, atherosclerosis, and arthritis (for reviews, see e.g. Schachter 1999; Elwell et al. 2016). The
mouse pathogen C. muridarum – previously called C. trachomatis mouse pneumonitis (MoPn) – is a
useful model of genital tract infections in humans.
Although chlamydial infections are treatable with antibiotics, many individuals go untreated, no
drug is sufficiently cost-effective for the elimination of the bacterium in developing nations, even
patients that are treated may develop chronic sequelae, and, somewhat paradoxically, countries that
have established screening programs, followed by antibiotherapy, have observed an increase in the
prevalence of the infection (Götz et al. 2002). This increase is thought to be due to a block in the
development of natural immunity as a result of antibiotherapy (Götz et al. 2002; Brunham et al. 2005).
The implementation of a vaccine is probably the best approach to control and eradicate these diseases
(de la Maza and Peterson 2002; Brunham and Rey-Ladino 2005; Rockey et al. 2009; Farris and
Morrison 2011), but producing an effective vaccine has thus far remained elusive (for a recent review,
see de la Maza et al. 2017).
All chlamydiae share a developmental cycle in which they alternate between extracellular,
infectious elementary bodies (EBs) and intracellular, noninfectious reticulate bodies (Fig. 15.1).
EBs enter mucosal cells and differentiate into reticulate bodies in a membrane-enclosed compartment
– the inclusion. After several rounds of replication, reticulate bodies redifferentiate into EBs and are
released from the host cell, ready to infect neighboring cells (Elwell et al. 2016).
Attempts to produce a vaccine against C. trachomatis were initiated in the 1960s (see Grayston
and Wang 1978, Igietseme et al. 2011, and references therein). Vaccines formulated with whole
inactivated and viable organisms were tested in humans and in nonhuman primates for protection
against trachoma. Several conclusions were reached from these studies. Some vaccine protocols
662
15 Biomedical Applications
along with the proteins used as immunogen and/or tags that will direct them toward specific cells or
associate them with particles used as carrier, so as to improve the uptake of target MPs. APol particles
resemble, to an extent, the polymeric micelles already used in some vaccine formulations (Trimaille
and Verrier 2015), some of which are based on hydrophobized poly(γ-glutamic acid), a category of
polymers which, as we have seen in Chap. 5 (Table 5.1), can be used as APols (Han et al. 2014). This
intriguing set of potential advantages prompted attempts at using APols in the formulation of vaccines
directed against a widely distributed pathogenic bacterium, C. trachomatis.
Chlamydiae are Gram-negative (Gram
À ) eubacteria, obligate intracellular pathogens, and
symbionts of diverse organisms, ranging from humans to amoebae (reviewed in Bachmann et al.
2014; Elwell et al. 2016). The best-studied group in the Chlamydiae phylum is the Chlamydiaceae
family, which comprises 11 species that are pathogenic to humans or animals. C. trachomatis and
C. pneumoniae, the major species that infect humans, are responsible for a wide range of diseases
(Schachter and Dawson 1978; Centers for Disease Control and Prevention 1999; Schachter 1999).
C. trachomatis is one of the most common human pathogens and is found in all regions of the world,
where it is the leading cause of sexually transmitted bacterial infections. It can produce ocular,
gastrointestinal, and respiratory infections, which can affect persons of all ages. In young individuals,
C. trachomatis is the most common sexually transmitted bacterial pathogen. Genital infections can
remain asymptomatic, but others can produce acute symptomatology. In women, long-term sequelae
such as infertility and ectopic pregnancy can develop. At birth, newborns can become infected in the
eyes and lungs if the mother has a genital tract infection at the time of delivery. In countries with poor
hygienic conditions, young children can have multiple ocular infections that result in the development
of trachoma later in life. C. trachomatis has also been isolated from the lungs of adults, in particular
from immunocompromised patients. Infection with C. trachomatis facilitates the transmission of HIV
and is associated with cervical cancer. C. pneumoniae causes respiratory infections, accounting for
~10% of community-acquired pneumonia, and is linked to a number of chronic diseases, including
asthma, atherosclerosis, and arthritis (for reviews, see e.g. Schachter 1999; Elwell et al. 2016). The
mouse pathogen C. muridarum – previously called C. trachomatis mouse pneumonitis (MoPn) – is a
useful model of genital tract infections in humans.
Although chlamydial infections are treatable with antibiotics, many individuals go untreated, no
drug is sufficiently cost-effective for the elimination of the bacterium in developing nations, even
patients that are treated may develop chronic sequelae, and, somewhat paradoxically, countries that
have established screening programs, followed by antibiotherapy, have observed an increase in the
prevalence of the infection (Götz et al. 2002). This increase is thought to be due to a block in the
development of natural immunity as a result of antibiotherapy (Götz et al. 2002; Brunham et al. 2005).
The implementation of a vaccine is probably the best approach to control and eradicate these diseases
(de la Maza and Peterson 2002; Brunham and Rey-Ladino 2005; Rockey et al. 2009; Farris and
Morrison 2011), but producing an effective vaccine has thus far remained elusive (for a recent review,
see de la Maza et al. 2017).
All chlamydiae share a developmental cycle in which they alternate between extracellular,
infectious elementary bodies (EBs) and intracellular, noninfectious reticulate bodies (Fig. 15.1).
EBs enter mucosal cells and differentiate into reticulate bodies in a membrane-enclosed compartment
– the inclusion. After several rounds of replication, reticulate bodies redifferentiate into EBs and are
released from the host cell, ready to infect neighboring cells (Elwell et al. 2016).
Attempts to produce a vaccine against C. trachomatis were initiated in the 1960s (see Grayston
and Wang 1978, Igietseme et al. 2011, and references therein). Vaccines formulated with whole
inactivated and viable organisms were tested in humans and in nonhuman primates for protection
against trachoma. Several conclusions were reached from these studies. Some vaccine protocols
662
15 Biomedical Applications