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          cell-mediated immune response of chickens is related to the IBDV   of vaccination against the disease. Of course, vvIBDV or variant
          strain. Currently our knowledge on T-cell response to IBDV   IBDV strains transmitted into the vaccinated flocks from outside
          infection is quite limited, and the viral components of IBDV that   is always number 1 threat to poultry farms. Up to now, a variety of
          carry dominant protective epitopes for T-cell activation have not   vaccines have been developed and commercially available to prac-
          determined so far. Overall, the role of cell-mediated immunity in   tical use, such as attenuated live IBDV vaccines, inactivated IBDV
          chicken response to IBDV infection is very important but needs   vaccines, IBDV immune complex vaccines, genetic engineering
          to be further elucidated.                             vaccines, and subunit vaccines. DNA vaccines used to hold a great
                                                                promise for the prevention and control of infectious diseases due
          Suppression of chicken immune response                to its convenience in storage and transportation, but its efficacy
          by IBDV                                               is far from expectation. Right now, it is clear that immunization
          As described above, BF is the central immune organ of poultry   of animals with DNA vaccines requires boosts, and one of the
          that is responsible for the development and maturation of B cells   boosts should be completed with protein antigens encoded by
          and the generation of diverse antibody repertoire in young chick-  the DNA vaccine. Priming with DNA vaccine and boosting with
          ens, any damage to BF would affect humoral immune response   inactivated vaccine conferred satisfactory protection of chickens
          of chickens to antigens. Suppression of chicken humoral immu-  against infectious bursal disease (Hsieh et al., 2007). However,
          nity is the most distinctive feature of IBDV infection. As BF is   DNA vaccination with VP2 gene fragment only conferred 75%
          the target organ of IBDV, IBDV infection induces apoptosis in   protection against virulent IBDV (vIBDV) challenge in chickens
          proliferating B lymphocytes in BF, directly causing a rapid, pro-  (Pradhan et al., 2014). Currently, no DNA vaccine is commer-
          gressive loss of B lymphocytes as observed in the bursal cortex   cially available for the prevention and control of chicken diseases.
          and medulla, peripheral blood and thymic medulla, leading to the
          suppression of humoral immunity, which makes chickens vulner-  Attenuated live IBDV vaccines
          able to secondary microbial infections.               Live attenuated IBDV vaccines are commercially available and
            There  might  be  multiple  mechanisms  involved  in  IBDV-  commonly used for the prevention and control of IBD. This type
          induced suppression of immune response in chickens. During the   of vaccines is generally developed by attenuating the virulence of
          acute phase of IBDV infection, IBDV employs different strate-  IBDV strains isolated from IBD outbreaks via serial passages of
          gies  to  dampen  antiviral  response  via  suppressing  type  I  IFN   the field isolate in tissue culture or embryonated eggs. However,
          expressions and MDA5-dependent signalling pathway, hijacking   the timing for vaccination with a live vaccine is critical because
          autophagic vacuoles, and inducing apoptosis in host cells, which   maternally derived antibodies or circulating anti-IBDV antibod-
          facilitates viral replication and spreading in BF. As a consequence,   ies in chickens neutralize the vaccine. If the timing for vaccination
          both innate and adaptive immune responses in infected chickens   is inadequate, the titre of antibodies against IBDV cannot reach
          are suppressed, and the immune system of survival chickens   an optimal level, which might require revaccinations for safety. To
          may not be fully functional even after recovery from the disease,   be noted, vvIBDV can establish an infection in chickens with anti-
          resulting in diminished Ab production following vaccination   bodies after immunization with highly attenuated vaccine strains.
          against other microbial diseases and increased susceptibility to   While administration with less attenuated strains (‘hot vaccines’)
          secondary microbial infections. Of note, vaccination of chickens   can provide protection, this type of vaccine causes severer lesions
          with live IBDV vaccines might also cause more or less damages to   in the BF than highly attenuated vaccine strains (Müller et al.,
          BF, which could diminish the expected titres of antibodies after   2003), leading to immunosuppression in vaccinated chickens to
          administration with NDV or AIV vaccines.              a certain degree, and affecting their immune response to other
                                                                vaccines, such as NDV or avian influenza vaccines. One of the
                                                                potential hazardous outcomes from administration of live attenu-
          Control of IBD by vaccination                         ated vaccines might be the ‘revert to virulence’ or generation of
          IBD remains a severe economic threat to the poultry industry   a new viral strain via recombination between vaccine strain and
          across the globe. IBDV is highly contagious and resistant to   circulating wild IBDV strains.
          inactivation with disinfectants. Once IBD occurs in flocks, the
          virus persists and remains infective in poultry house for several   Inactivated IBDV vaccines
          months or longer even after the infected chickens are removed.   The IBDV strains used for the development of inactivated IBDV
          Vaccination is absolutely required for the prevention and control   vaccines are usually isolated from diseased chickens in an out-
          of this disease. On poultry farms with strict hygiene management,   break of IBD. Inactivated IBD vaccine must have a high antigenic
          immunization of chickens with vaccines for the control of this   content (concentrated IBDV) in order to induce strong humoral
          disease is often proven to be successful, but not always, because   immunity in breeding adult chickens (maternally derived anti-
          it is not uncommon to see some diseased chickens associated   bodies) that helps protecting the progeny from IBDV infection.
          with IBDV infection and even an outbreak of IBD in the flocks.   As the maternally derived antibodies in newly hatched progeny
          Although the reason for the unexpected outbreak of this disease   chicks can neutralize the live IBDV vaccines when administered
          in vaccinated flocks is not very clear, the genetic mutations in   too early, the timing for vaccination of chicks with live IBDV vac-
          the hypervariable region of circulating IBDV VP2 might be   cines is a crucial factor affecting immune response. In contrast to
          attributable under the immune pressure, resulting in the failure   live IBDV vaccines, the efficacy of inactivated IBDV vaccines is
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