Page 345 - Avian Virology: Current Research and Future Trends

336 | Coppo et al.

are higher and so eye-drop vaccination is generally restricted to comparison of full genome sequences of TCO and CEO ILT vac-
the longer-lived birds, such as layer and breeder birds. cine strains used in the USA, and the same vaccines strains after
As attenuated ILTV vaccines are produced through sequential 20 sequential passages in SPF chickens, revealed that a mutation
passage of virus through eggs and/or cell culture, rather than in the UL41 gene was likely to be responsible for the increase in
the targeted deletion of virulence factors, the molecular basis of virulence in the CEO vaccine after passage. The increase in viru-
attenuation of these vaccines remains poorly defined. Genotyp- lence in the TCO vaccine after passage was not as dramatic but
ing systems that aimed to distinguish between different strains of could potentially be associated with deletions in the copy number
ILTV by analysing regions of the ILTV genome using PCR-RFLP of a repeat sequence in the promoter region of ICP4 (García et
or sequence based methods provided the first glimpses of genetic al., 2013b).
differences between vaccine strains and virulent field strains,
although a high degree of similarity between vaccine and field Vectored vaccines
strains was frequently observed (Kotiw et al., 1982, 1986; Kirk- Vectored ILTV vaccines have been recently developed and are
patrick et al., 2006b; Oldoni and García, 2007; Neff et al., 2008; available commercially. Their use is increasing in some poultry
Oldoni et al., 2008; Chacón et al., 2010; Blacker et al., 2011). producing areas, particularly in North America, however they are
More recently, full genome sequencing of vaccine and virulent not available in all countries (Coppo et al., 2013). These vaccines
field isolates of ILTV have allowed a more comprehensive exami- use other viruses as vectors (Fowlpox virus; FPV, or HVT) that
nation of the differences between vaccine strains and other ILTV express immunogenic ILTV proteins. A summary of the virally
strains. Key studies include whole genome sequencing and analy- vectored ILT vaccines that are currently commercially available is
sis of vaccine and field isolates from Australia (Agnew-Crumpton shown in Table 11.2.
et al., 2016; Lee, S.W. et al., 2011a,b, 2012), Italy (Piccirillo et These vectored vaccines can offer bivalent protection and can
al., 2016), USA (Chandra et al., 2012; Spatz et al., 2012; García avoid some of the limitations associated with the attenuated ILTV
et al., 2013a) and China (Kong et al., 2013; Zhao et al., 2015). vaccines, including bird-to-bird spread and reversion to virulence,
Individually these studies have identified some potential genetic latency, and potentially problems associated with recombination
features that could be associated with virulence (or attenuation) (Davison et al., 2006; Johnson et al., 2010; Gimeno et al., 2011;
among vaccine and virulent field strains in a region, but these Vagnozzi et al., 2012b). It is worth noting, however, that the HVT
have not been confirmed experimentally with mutagenesis or and FPV vectors are both from virus families in which recombi-
gene deletion studies, and frequently when sequence analyses are nation has been demonstrated, as are many commonly used viral
expanded to include all available genome sequences, the same vectors (Devlin et al., 2016). The consequences that may result
specific genetic features can be identified in both vaccine and from recombination involving these vectored vaccines have not
virulent isolates (García et al., 2013a; Piccirillo et al., 2016). To been explored (Devlin et al., 2016). Another advantage of these
further complicate these associations, some vaccine strains can vectored vaccines is their ability to be delivered by methods that
be as virulent as field strains when administered by similar routes are not available for attenuated vaccines. Specifically, these vac-
and at similar doses (Kirkpatrick et al., 2006a; Lee et al., 2015). cines can be delivered in ovo to chicken embryos at 18 days of
A clearer picture of the genetic basis of vaccine attenuation was incubation. This is a preferred method of administration for many
achieved in a study that compared the full genome sequences of poultry industries, particularly commercial broiler flocks, and can
two Australian origin ILTV vaccines strains; A20 and SA-2 (Lee result in more uniform vaccine delivery (Williams and Zedek,
et al., 2011b). The A20 strain was derived from the SA-2 strain by 2010). This, however, needs to be balanced against some of the
sequential passage of the virus in tissue culture in order to reduce limitations of these vaccines.
the level of residual virulence, which was confirmed experimen- Studies characterizing the FPV vectored ILT vaccine, and the
tally (Kirkpatrick et al., 2006a). Only two non-synonymous HVT vectored vaccine expressing the ILTV gI and gD proteins,
SNPs were identified when the genomes of A20 and SA-2 ILTV have been reported in the peer-reviewed literature, but similar
were compared. It is likely that these two SNPs, in the ORF B studies examining the HVT vectored vaccine expressing ILTV gB
and UL15 genes, are related to the higher level of attenuation of are currently not available (Table 11.2). In general, the level of
A20, compared with SA-2 (Lee et al., 2011b). In another study, protection induced by the vectored vaccines appears to be lower

Table 11.2 Virally vectored ILT vaccines in commercial use
Viral vector Expressed ILTV antigens Route of administration References
FPV a Glycoprotein B, UL-32 Wing-web puncture, in ovo Davison et al. (2006); Johnson et al. (2010); Vagnozzi et al. (2012b); Godoy
et al. (2013)
HVT b Glycoproteins I and D Subcutaneous, in ovo Johnson et al. (2010); Gimeno et al. (2011); Vagnozzi et al. (2012b)
HVT c Glycoprotein B Subcutaneous, in ovo Godoy et al. (2013)

a Vectormune® FP-LT.
b Innovax®–ILT.
c Vectormune® HVT-LT.