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308  |  Corredor and Nagy

          Inc). Other commercial vaccines preparations include FAdV-11   demonstrates the practicality and applicability of fowl adeno-
          (e.g. Farvet).                                        viruses as vectors for the production of poultry vaccines and as
            The use of recombinant DNA technology has allowed the   vehicles for gene delivery.
          development of new candidate vaccines during the last 10 years.
          The penton base subunit vaccine (Shah et al., 2012) and fibre-2
          protein of FAdV-4 (patent publication US 20160193323 A1)   Perspectives
          have been developed to control HPS. Other candidate vaccines   The taxonomy of adenoviruses is constantly changing and thus
          for HPS/IBH or GE include fibre-2 protein of FAdV-A, fibre   the assignation of new species groups and inclusion of some yet-
          protein of FAdV-B, FAdV-D and FAdV-E (patent publication WO   to-be-classified viruses in any of the genera are to be expected.
          2015024929 A3). A live-attenuated vaccine has been developed   The growing number of epizootiological studies and reports of
          by propagation of chicken embryo-adapted FAdV-4 (Mansoor et   novel  molecular  methods  for  diagnosis  have  provided  further
          al., 2011).                                           insights into virus-induced pathogenesis, virulence factors and
                                                                prevalence. These studies will continue and be fundamental for
                                                                the identification of potential virulence factors and development
          Aviadenovirus as vaccine and gene delivery            of effective vaccines for disease control. Further advances in
          vector                                                molecular cloning will allow the rapid and efficient generation of
          Mammalian  adenoviruses  are best  characterized  and used  as   new virus-based vectors for applications in gene delivery and vac-
          vectors for various purposes such as gene delivery, vaccina-  cine development. Due to their large genome with dispensable
          tion, and oncolytic therapeutics (Wold and Toth, 2013). Fowl   regions for in vitro replication, aviadenoviruses are expected to be
          adenoviruses are less characterized, though their potential as   the most used platforms for the development of monovalent and
          vaccine vectors have been demonstrated. Owing to the larger   multivalent vaccines for poultry. Lastly, further studies on viral
          size and gene arrangements of their genomes, the FAdVs have   gene function will reveal novel mechanisms by which the virus
          considerable capacity for foreign gene insertion. Recombinant   modulates the host cell to favour its own replication and provide
          viruses were generated using various insertion sites by replacing   further understanding on the molecular basis of virus-induced
          non-essential regions at the right ends of the genomes of FAdV-1,   pathogenesis.
          FAdV-8, FAdV-9, and FAdV-10 (Sheppard et al., 1998b; Michou
          et al., 1999; François et al., 2001; Ojkic and Nagy, 2001; John-  References
          son et al., 2003). The FAdV-1 based vaccine expressing the VP2   Abe, T., Nakamura, K., Tojo, T., and Yuasa, N. (2001). Gizzard erosion in
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          protein of IBDV provided protection against challenge (Francois   Adair, B.M., Todd, D., McFerran, J.B., and McKillop, E.R. (1986).
          et al., 2004). The S1 gene of infectious bronchitis virus (IBV)   Comparative serological studies with egg drop syndrome virus. Avian
          incorporated into the genome of FAdV-8 was shown to provide   Pathol. 15, 677–685.
          protection (Johnson et al., 2003). Moreover, the chicken inter-  Ahmad, M.U., and Burgess, G.W. (2001). Production and characterization of
          feron gamma was successfully expressed in the FAdV-8 CFA40   monoclonal antibodies to fowl adenoviruses. Avian Pathol. 30, 457–463.
                                                                   https://doi.org/10.1080/03079450120078635
          strain (Johnson et al., 2000). An infectious clone of FAdV-9 was   Alexander, H.S., Huber, P., Cao, J., Krell, P.J., and Nagy, E. (1998). Growth
          generated and proved invaluable for genetic studies and vaccine   characteristics of fowl adenovirus type 8 in a chicken hepatoma cell line.
          development (Ojkic and Nagy, 2001). Deletion of a 2.4 kb region   J. Virol. Methods 74, 9–14.
          at the left end region and replacement with foreign genes resulted   Alvarado, I.R., Villegas, P., El-Attrache, J., Jensen, E., Rosales, G., Perozo,
                                                                   F., and Purvis, L.B. (2007). Genetic characterization, pathogenicity,
          in recombinant viruses that elicited immune responses in chickens   and protection studies with an avian adenovirus isolate associated with
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          Gay et al., 2015). Recently, an FAdV-9-based dual-site expression   Anderson, K.P., and Fennie, E.H. (1987). Adenovirus early region 1A
                                                                   modulation of interferon antiviral activity. J. Virol. 61, 787–795.
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            FAdV-1 and FAd-9, and likely all avian adenoviruses, lead to   Asthana, M., Chandra, R., and Kumar, R. (2013). Hydropericardium
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          1999; Ojkic and Nagy, 2001; Corredor and Nagy, 2010b). FAdVs   (1993). Evaluation of cell culture propagated and in vivo propagated
          have  also been demonstrated as  potential  cancer therapeutics.   hemorrhagic enteritis vaccines in turkeys. Vet. Immunol. Immunopathol.
                                                                   35, 375–383.
          For example, survival of C57BL/6 mice carrying B16 melanoma   Barra, C., and Langlois, P. (2009). First step in characterization of cis-acting
          and tumour regression increased upon intratumoural injections   sequences involved in fowl adenovirus 1 (CELO) packaging and its
          of FAdV-1 expressing the human interleukin 2 (Cherenova et   effect on the development of a helper-dependent vector strategy. Virus
                                                                   Genes 38, 46–55. https://doi.org/10.1007/s11262-008-0281-6
          al., 2004). The same antitumoral properties were reported using   Bartha, A. (1984). Dropped egg production in ducks associated with
          FAdV-1  expressing  the  herpes  simplex  virus  thymidine  kinase   adenovirus infection. Avian Pathol. 13, 119–126.
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