Page 346 - Avian Virology: Current Research and Future Trends

Infectious Laryngotracheitis Virus | 337

than the protection induced by attenuated vaccines. The vectored used as an adjuvant for ILTV vaccines (Tong et al., 2001; Sun et
vaccines can provide good protection against disease, but do al., 2008; Chen et al., 2011a,b).
not appear to protect against infection with field viruses as well Deletion mutant ILTV vaccine candidates have also been
as attenuated vaccines, potentially because they do not replicate generated and tested in vaccination and challenge studies. These
in the target organs within the respiratory tract (Johnson et al., are summarized in Table 11.3. The first of these mutants, a TK
2010; Gimeno et al., 2011; Vagnozzi et al., 2012b). The use of vac- deletion mutant, was described over 20 years ago (Schnitzlein et
cines that prevent disease, but not infection, allows field viruses to al., 1995). Three of the more recently examined deletion mutants,
infect and circulate in vaccinated flocks and presents a risk to any deficient in ORF C, gG or gJ, have demonstrated marked attenu-
unvaccinated or incompletely vaccinated birds in the flock, or in ation in vivo, a high level of immunogenicity, the potential to be
neighbouring flocks. Vaccines that prevent disease, but not infec- utilized in DIVA control strategies and some have the potential to
tion, have been termed ‘imperfect’ or ‘leaky’ vaccines (Gandon be delivered in ovo (Fuchs et al., 2005; Devlin et al., 2007; Pavlova
et al., 2001). It is possible that such vaccines allow more virulent et al., 2010; Legione et al., 2012; Mashchenko et al., 2013; García
strains of field viruses to persist and spread in vaccinated popu- et al., 2016). This combination of features makes these deletion
lations. This imperfect vaccine hypothesis was first described mutants promising vaccine candidates. The UL0 deletion mutant
more than a decade ago (Gandon et al., 2001) but has recently of ILTV has been used as a vaccine vector to express antigens from
been demonstrated experimentally in chickens in the context avian influenza virus. This approach was successful in achieving
of vaccines for Marek’s disease virus (Read et al., 2015). Similar bivalent protection, demonstrating the potential for ILTV to be
studies for vaccines against ILTV have not been performed, but used a vector for poultry vaccines (Veits et al., 2003b; Pavlova
the increasing use of ‘leaky’ ILTV vaccines warrant these studies et al., 2009). An additional advantage of these deletion mutant
being undertaken in the future. vaccines is their potential to be administered in ovo, as has been
demonstrated under experimental settings for the gG (Legione et
New approaches to vaccine development al., 2012) and ORF C (Schneiders et al., 2018) deletion mutants.
and use However, there are concerns that the presence of maternal anti-
Other vectored ILT vaccines are currently undergoing develop- body in the vaccinated embryos may have a detrimental effect on
ment and testing. These include vectored vaccines that utilize the efficacy of vaccination (Schneiders et al., 2018).
NDV as a vector to express ILTV gB, gD and gC, either individu- A challenge for all ILTV vaccines is the lack of any easily
ally, or in combination. Of these, the construct expressing ILTV measurable correlate of protection. It is therefore difficult to
gD has been shown to induce the highest level of protection fol- determine the success of any ILTV vaccination programs that
lowing challenge (Kanabagatte Basavarajappa et al., 2014; Zhao have performed in the field, and thus difficult to determine the
et al., 2014; Yu et al., 2017). Very virulent MDV has also been level of protection afforded by vaccination. Serology (ELISA) to
used as a vector to express ILTV glycoproteins, after first being detect serum antibody to ILTV is frequently performed to assess
attenuated by deletion of the MEQ oncogene. Two constructs exposure to vaccines, however serum antibody levels are not cor-
have been generated and tested, one expressing ILTV gB and related with protection against disease (Fahey et al., 1983). More
the other expressing ILTV gJ. The construct expressing gB was recently, detection of ILTV in feather shafts has been proposed as
shown to induce a comparable level of protection to that induced a novel method to assess vaccine uptake (Davidson et al., 2018),
by a commercial HVT vectored ILT vaccine (Gimeno et al., but this method also will not provide information about the
2015). In China, researchers have used FPV to express ILTV gB, protection status of a flock. Instead, cell-mediated immunity is
either alone or in combination with NDV proteins, or ILTV gB associated with protection (Honda et al., 1994). The future devel-
in conjunction with chicken interleukin 18 (IL-18) The vaccine opment of assays to measure cell-mediated immune responses
containing chicken IL-18 showed improved protection following following vaccination would greatly assist in optimizing the use of
challenge, demonstrating the potential for chicken IL-18 to be ILT vaccines (see ‘Pathogenesis and immunity’).

Table 11.3 ILTV deletion mutant candidate vaccines
Deleted gene References
Thymidine kinase Schnitzlein et al. (1995); Han et al. (2002)
UL0 Veits et al. (2003b)
UL47 Helferich et al. (2007b)
ORF C Garcia et al. (2016)
Glycoprotein C Pavlova et al. (2010)
Glycoprotein J Fuchs et al. (2005); Mashchenko et al. (2013)
Glycoprotein G Devlin et al. (2007); Devlin et al. (2008); Coppo et al. (2011); Legione et al. (2012)