Page 67 - Avian Virology: Current Research and Future Trends

60 | Samal

2007) and Texas GB (Paldurai et al., 2014a). A PPMV-1 (strain any empty vector. NDV accommodates foreign genes (at least
AV324) has also been rescued (Dortmans et al., 2009). 5.0 kb in length) with a good degree of stability (our unpublished
Reverse genetics has greatly improved our understanding of results). A single NDV vector can also be used to express two dif-
NDV molecular biology and pathogenesis. This system has also ferent foreign genes (Khattar et al., 2015a; Hu et al., 2018).
allowed us to engineer improved NDV vaccines, vaccine vectors, NDV is an ideal vaccine vector for poultry. Live attenuated
and improved oncolytic NDVs. NDV vaccines are widely used all over the world. Therefore, a live
attenuated NDV carrying the protective antigen of another avian
pathogen can be used as a bivalent vaccine. Such a vaccine will be
NDV as a vaccine vector economical for the poultry industry. NDV replicates efficiently in
NDV has several characteristics that make it an attractive vaccine the respiratory tract of chickens and induces strong local and sys-
vector for both human and animal uses (Kim and Samal, 2016). temic immune responses. Therefore, it will also induce a strong
Avirulent NDV strains are highly safe in avian and non-avian spe- immune response to the foreign antigen. Recombinant NDV has
cies. NDV replicates well in vivo and induces a robust immune been used to express the VP2 protein of infectious bursal disease
response. In contrast to adeno, herpes, and pox virus vectors virus (Huang, Z. et al., 2004b), HA protein of highly pathogenic
whose genome encodes many proteins, NDV encodes only seven avian influenza virus (Park et al., 2006; Ge et al., 2007; Römer-
proteins and thus there is less competition for immune responses Oberdörfer et al., 2008; Nayak et al., 2009), glycoprotein genes
between vector proteins and the expressed foreign antigen. NDV of infectious laryngotracheitis virus (Basavarajappa et al., 2014;
replicates in the cytoplasm and does not integrate into the host Zhao et al., 2014), the S, S1 and S2 proteins of infectious bronchi-
cell DNA. Recombination involving NDV either does not occur tis virus (Toro et al., 2014; Zhao et al., 2017; Shirvani et al., 2018),
or occurs rarely. NDV has a modular genome that facilitates and the F and G proteins of avian metapneumovirus subtype C
genetic manipulation. NDV infects via the intranasal route and (Hu et al., 2017).
therefore induces both mucosal and systemic immune responses. Several special features make NDV a promising vaccine vector
A wide range of NDV strains exists that can be used as vaccine for humans. NDV is not a natural human pathogen and is highly
vectors. attenuated in humans due to natural host range restriction. NDV
To insert a foreign gene into NDV genome for expression the is known to induce very high type I IFN levels in mammalian
following requirements must be fulfilled: cells (Honda et al., 2003), which contributes to an effective B cell
response to this virus and to the foreign antigen (Grieves et al.,
1 The sequence of the foreign gene should be analysed to 2018). Clinical trials for cancer treatment have also shown that
ensure that the NDV GS and GE like sequences and poly- high doses of NDV is safe in humans with very few side effects
merase slippage sequences are not present, which would (Fournier and Schirrmacher, 2013). Another advantage is that
affect the expression of the foreign gene. If present, these most humans do not have pre-existing immunity to NDV. The
sequences must be changed by silent mutagenesis. potential of NDV as a vaccine vector for human pathogens has
2 The ORF of the foreign gene must be flanked by NDV GS and already been evaluated in non-human primates (Bukreyev et al.,
GE sequences for recognition by the NDV RNA-dependent- 2005; DiNapoli et al., 2007a,b). The potential of recombinant
RNA-polymerase. NDV as a vaccine vector against human pathogens such as,
3 The insertion of the foreign gene cassette must meet the ‘rule influenza virus (Nakaya et al., 2001), highly pathogenic avian
of six’ requirement for efficient replication (Calain and Roux, influenza virus (Park et al., 2006; DiNapoli et al., 2007b, 2010),
1995). Therefore, if necessary, additional nt can be added measles virus (Kim et al., 2011), human immunodeficiency virus
at downstream of the foreign gene ORF to make the final (Carnero et al., 2009; Khattar et al., 2015a,b), severe acute respira-
genome length a multiple of six. tory syndrome-associated coronavirus (DiNapoli et al., 2007a),
human parainfluenza virus type 3 (Bukreyev et al., 2005), human
In general, a foreign gene flanked by NDV GS and GE respiratory syncytial virus (Martinez-Sobrido et al., 2006), Nipah
sequences is inserted into a 3′ non-coding region of an NDV virus (Kong et al., 2012), Ebola virus (Bukreyev et al., 2007),
genome as an additional transcription unit that is transcribed Norovirus (Kim et al., 2014b), and Borrelia burgdorferi (Xiao et
into an additional mRNA. Due to a polar gradient transcription, al., 2011).
foreign genes are expressed more efficiently when placed closer The potential of NDV as a vaccine vector for veterinary
to 3′-end of the genome. Although a foreign gene can be placed pathogens has also been explored. Recombinant NDV express-
between any two genes of NDV, the insertion site between the P ing the glycoprotein D (gD) of bovine herpesvirus 1 (BHV-1)
and M genes has been found optimal for efficient expression of conferred partial protection against virulent BHV-1 challenge in
the foreign protein and replication of NDV (Nakaya et al., 2001; calves (Khattar et al., 2010). A NDV-vectored vaccine express-
Zhao and Peters, 2003; Carnero et al., 2009; Zhao et al., 2015). ing glycoproteins Gn and Gc of Rift valley fever virus (RVFV)
The insertion of a foreign gene into NDV genome increases its protected mice against RVFV challenge and elicited neutralizing
genome length and gene number and often has a growth retar- antibody response in lambs (Kortekaas et al., 2010a). It was fur-
dation effect on virus replication in vitro and in vivo (Bukreyev ther shown that a NDV vectored vaccine only expressing RVFV
et al., 2006). It is critical that the recombinant virus containing Gn glycoprotein elicited neutralizing antibodies against RVFV in
the foreign gene is plaque purified to make sure it does not carry calves (Kortekaas et al., 2010b). An NDV vector expressing the