Vaccines and vaccination against IBDV

Vaccination is widely used to prevent IBD outbreaks in the field. Most of the commercially available vaccines against IBDV are live attenuated and inactivated ones; recombinant and subunit vaccines have been licensed in some countries.

Live vaccines are produced from classical and variant IBDV strains by passaging these viruses in tissue cultures or embryonated chicken eggs (YAMAGUCHI et al.

1996a; LASHER et al. 1997; JACKWOOD u. SOMMER-WAGNER 2011). They can be classified as mild, intermediate or intermediate plus vaccines based on the level of attenuation and residual virulence for SPF chickens (VAN DEN BERG et al. 2000a).

The intermediate plus vaccines are regularly applied to protect chickens against vvIBDV challenges. The Deventer formula may help to determine the optimal time for IBDV vaccination to circumvent the neutralizing activity of MAB (DE WIT 1998). Live vaccines are favourable for mass application through drinking water and can induce strong humoral and cellular immunity (MÜLLER et al. 2003; MÜLLER et al. 2012).

The proven reversion to virulence (YAMAGUCHI et al. 2000) and their residual immunosuppressive effects (RAUTENSCHLEIN et al. 2005b; RAUTENSCHLEIN et al. 2007) are major safety concern of their extensive field applications. Breeder vaccination by priming with live vaccines and boosting with inactivated oil-emulsion vaccines prior to laying ensures higher levels of MAB transfer to the progeny (MAAS et al. 2001; MÜLLER et al. 2012) and is applied in some countries.

Commercially available IBD immune complex (IBD-ICX) vaccines are found to be safe and efficacious for in ovo and posthatch vaccination of broilers (HADDAD et al.

1997; GIAMBRONE et al. 2001; IVAN et al. 2005). They are prepared by combining an IBDV-hyperimmune serum with live intermediate plus IBDV (WHITFILL et al.

1995; JOHNSTON et al. 1997). The entrapment and retention of ICX on bursal follicular dendritic cells (FDCs) and on splenic FDCs in the germinal center were suggested as the immune enhancing mechanism of such vaccines (JEURISSEN et al. 1998). The viruses are released from the ICX when the levels of MAB declined to induce specific humoral immune responses that protect chickens against challenge

virus. A recombinant neutralizing Ab has been evaluated for formulation of an IBD-ICX vaccine (IGNJATOVIC et al. 2006).

The protective effects of many recombinant IBDV vaccines were evaluated under experimental and field conditions. The polyprotein (PP), mature VP2 or immunogenic domains of VP2 of pathogenic IBDV strains were targeted to produce candidate vaccines: subunit, vectored, virus-like particles (VLPs) and chimeric virus particles.

Some of these experimental vaccines are presented in table 4.

An IBDV-VP2 subunit vaccine expressed in Pichia pastoris is licensed for commercial uses (PITCOVSKI et al. 2003). An E. coli expressed subunit vaccine has been evaluated under field conditions (RONG et al. 2007). The use of peptide epitope mimics, i.e. mimotopes as candidate IBDV vaccines have become promising strategy. Mimotopes are chemically synthesized and resembled the neutralizing epitopes of VP2. Their expression in prokaryotic expression vector resulted in a bioactive peptide that can induce significant neutralizing Abs and protection against IBDV challenge (WANG et al. 2007). These types of vaccines induce strong humoral immunity and always require adjuvants and multiple injections for inducing protective levels of neutralizing Abs. Many live vectored IBDV vaccines, which mimic natural infection have been developed and tested for efficacy. A live Newcastle disease virus (NDV) vectored VP2 vaccine has been experimentally evaluated (HUANG et al.

2004) and recently HVT-IBD vaccine was licensed for in ovo and posthatch vaccination of broilers and layers in various countries (BUBLOT et al. 2007; LE GROS et al. 2009). These vectored vaccines induce strong systemic neutralizing Ab levels and mucosal Abs, but pre-existing immunity for example against NDV-vector may affect their efficacy.

Other IBDV-candidate vaccines include virus-like particles (VLPs). These vaccines lack viral genomes and are non-infectious. They preserve the native conformation of the capsid protein and present multiple copies of these immunogenic epitopes (BRUN et al. 2011). However, the expression systems determine the nature of the VLPs. The expression of IBDV PP by a recombinant vaccinia virus in mammalian

cells resulted in true VLPs (FERNANDEZ-ARIAS et al. 1998), whereas defective VLPs were detected when the PP was expressed in insect cells by a baculovirus (HU et al. 1999; KIBENGE et al. 1999; CHEVALIER et al. 2002). The main reason for the lack of true VLP formation in the yeast and insect cells may be the absence of the host protease, puromycin-sensitive aminopeptidase that is required for the processing of the PP (IRIGOYEN et al. 2012). The VP2 icosahedral capsid had been shown to induce the higher neutralizing Ab levels and better protection against IBDV challenge than the PP-derived structures and the VPX tubules (MARTINEZ-TORRECUADRADA et al. 2003).

Candidate attenuated live IBDV vaccines generated by reverse genetics have been shown to induce strong protective immunity (BOOT et al. 2002; MUNDT et al. 2003;

ZIERENBERG et al. 2004; QIN et al. 2010; GAO et al. 2011), but vaccinated chickens developed milder bursal lesions after a challenge study. These tailored chimeric IBDV vaccines were generated to contain VP2 regions of two different strains of serotype 1 IBDV (MUNDT et al. 2003; GAO et al. 2011) or were chimeric between segment A of serotype 1 and segment B of serotype 2 IBDVs (ZIERENBERG et al. 2004). A VP5 mutant IBDV vaccine induced better protection than its molecular cloned PP counterpart (QIN et al. 2010). BOOT et al. (2002) produced a chimeric virus containing the C-terminal serotype 2 VP3 inserted into genome segment A of serotype 1 IBDV. Nevertheless, the risk of reversion to virulence of these genetically modified viruses hinders their field applications (RAUE et al. 2004).

Recombinant IBDV-VP2 vaccines may possibly be used as ‘’marker vaccines’’

(MÜLLER et al. 2012) by allowing the differentiation of infected from vaccinated animals (DIVA) by the detection of anti-VP3 Abs in naturally infected birds.

Table 4: Experimental IBDV vaccines

Subunit hVP2 Pichia pastoris 30% morbidity and mortality, IBDV Ag detected

in the bursa

(VILLEGAS et al. 2008)

N-terminal VP2 (aa 18–139) E. coli ↑ELISA-Ab titer, 100% protection from mortality, IBDV Ag detected in the bursa

(PRADHAN et al. 2012)

Mimotope E. coli ↑ELISA- and VN-Ab titer, 100% survival rate (WANG et al. 2007)

VP2 Plants Seroconverted, 80% protection from mortality (WU et al. 2004; WU et al. 2007b) Chimeric virus

particles

Neutralizing epitope from the PBC loop

Bamboo mosaic virus ↑ ELISA-Ab titer, mild to moderate bursal lesions (CHEN et al. 2012b)

Mimotope polypeptide Human hepatitis B virus ↑ELISA- and VN-Ab titer, 100% survival rate (WANG et al. 2012c) Live vectored

virus

VP2 Fowlpox virus 14% and 33% of the chickens protected from

gross and histological lesions, respectively

(TSUKAMOTO et al. 2000)

Marek’s disease virus 55% protection from bursal lesions, IBDV infection was not prevented

(TSUKAMOTO et al. 1999)

Semliki forest virus Some levels of neutralizing Abs detected (PHENIX et al. 2001) Vaccinia virus VN-Ab titer demonstrated (ZANETTI et al. 2012) Avian adenovirus ↑VN-Ab titer, mortality up to 20% (FRANCOIS et al. 2004) T4 bacteriophage Ab detected, partial protection (CAO et al. 2005) Live

bacterial-delivered

VP2 E. coli Over 95% protection from mortality,

seroconversion detected

(MAHMOOD et al. 2007)

PP S. Typhimurium 73% protection from mortality and

seroconversion detected

(LI et al. 2006)