Avian adenovirus CELO recombinants expressing VP2 of infectious bursal disease virus induce protection against bursal disease in chickens

François, Achille; Chevalier, Christophe; Delmas, Bernard; Eterradossi, Nicolas; Toquin, D.; Rivallan, G.; Langlois, Patrick

doi:10.1016/j.vaccine.2003.10.039

Cited by 69 publications

(34 citation statements)

References 32 publications

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“…This initiated interest in the development of nonhuman AdVs, including FAdVs, which are an attractive choice both as vaccine vectors for poultry (15,16) and as gene therapy vectors. The optimization of delivery routes and application regimens of AdV vectors are also needed to counteract the limitations of HAdV-based vaccines (21).…”

Section: Discussionmentioning

confidence: 99%

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Oral Inoculation of Chickens with a Candidate Fowl Adenovirus 9 Vector

Deng

Sharif

Nagy

2013

Clin Vaccine Immunol

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Fowl adenoviruses (FAdVs) are a potential alternative to human adenovirus-based vaccine vectors. Our previous studies demonstrated that a 2.4-kb region at the left end of the FAdV-9 genome is nonessential for virus replication and is suitable for the insertion or replacement of transgenes. Our in vivo study showed that the virus FAdV-9⌬4, lacking six open reading frames (ORFs) at the left end of its genome, replicates less efficiently than wild-type FAdV-9 (wtFAdV-9) in chickens that were infected intramuscularly. However, the fecal-oral route is the natural route of FAdV infection, and the oral administration of a vaccine confers some advantages compared to administration through other routes, especially when developing an adenovirus as a vaccine vector. Therefore, we sought to investigate the effects of FAdV-9 in orally inoculated chickens. In the present study, we orally inoculated specific-pathogen-free (SPF) chickens with FAdV-9 and FAdV-9⌬4 and assessed virus shedding, antibody response, and viral genome copy number and cytokine gene expression in tissues. Our data showed that FAdV-9⌬4 replicated less efficiently than did wtFAdV-9, as evidenced by reduced virus shedding in feces, lower viral genome copy number in tissues, and lower antibody response, which are consistent with the results of the intramuscular route of immunization. Furthermore, we found that both wtFAdV-9 and FAdV-9⌬4 upregulated the mRNA expression of alpha interferon (IFN-␣), IFN-␥, and interleukin-12 (IL-12). In addition, there was a trend toward downregulation of IL-10 gene expression caused by both viruses. These findings indicate that one or more of the six deleted ORFs contribute to modulating the host response against virus infection as well as virus replication in vivo.

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Section: Discussionmentioning

confidence: 99%

“…FAdVs are also suitable vectors; for example, FAdV-1-and FAdV-8-based recombinant viruses have induced protective immune responses against infectious bursal disease virus and infectious bronchitis virus, respectively (15,16).…”

mentioning

confidence: 99%

Oral Inoculation of Chickens with a Candidate Fowl Adenovirus 9 Vector

Deng

Sharif

Nagy

2013

Clin Vaccine Immunol

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“…In addition to attenuated or inactivated IBDV-based vaccines (23), VP2 expression provides complete protection against IBDV (24)(25)(26). Tϭ1 SVPs have also been used as vaccine carriers to target diseases such as cancer, after incorporation of a 54-residue E7 oncoprotein fragment of human papillomavirus 16 to the VP2 C terminus (27).…”

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confidence: 99%

Structural Basis for the Development of Avian Virus Capsids That Display Influenza Virus Proteins and Induce Protective Immunity

Pascual

Mata

Gómez-Blanco

et al. 2015

J Virol

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Bioengineering of viruses and virus-like particles (VLPs) is a well-established approach in the development of new and improved vaccines against viral and bacterial pathogens. We report here that the capsid of a major avian pathogen, infectious bursal disease virus (IBDV), can accommodate heterologous proteins to induce protective immunity. The structural units of the ϳ70-nmdiameter T‫31؍‬ IBDV capsid are trimers of VP2, which is made as a precursor (pVP2). The pVP2 C-terminal domain has an amphipathic ␣ helix that controls VP2 polymorphism. In the absence of the VP3 scaffolding protein, 466-residue pVP2 intermediates bearing this ␣ helix assemble into genuine VLPs only when expressed with an N-terminal His 6 tag (the HT-VP2-466 protein). HT-VP2-466 capsids are optimal for protein insertion, as they are large enough (cargo space, ϳ78,000 nm 3 ) and are assembled from a single protein. We explored HT-VP2-466-based chimeric capsids initially using enhanced green fluorescent protein (EGFP). The VLP assembly yield was efficient when we coexpressed EGFP-HT-VP2-466 and HT-VP2-466 from two recombinant baculoviruses. The native EGFP structure (ϳ240 copies/virion) was successfully inserted in a functional form, as VLPs were fluorescent, and three-dimensional cryo-electron microscopy showed that the EGFP molecules incorporated at the inner capsid surface. Immunization of mice with purified EGFP-VLPs elicited anti-EGFP antibodies. We also inserted hemagglutinin (HA) and matrix (M2) protein epitopes derived from the mouse-adapted A/PR/8/34 influenza virus and engineered several HA-and M2-derived chimeric capsids. Mice immunized with VLPs containing the HA stalk, an M2 fragment, or both antigens developed full protection against viral challenge. IMPORTANCEVirus-like particles (VLPs) are multimeric protein cages that mimic the infectious virus capsid and are potential candidates as nonliving vaccines that induce long-lasting protection. Chimeric VLPs can display or include foreign antigens, which could be a conserved epitope to elicit broadly neutralizing antibodies or several variable epitopes effective against a large number of viral strains. We report the biochemical, structural, and immunological characterization of chimeric VLPs derived from infectious bursal disease virus (IBDV), an important poultry pathogen. To test the potential of IBDV VLPs as a vaccine vehicle, we used the enhanced green fluorescent protein and two fragments derived from the hemagglutinin and the M2 matrix protein of the human murine-adapted influenza virus. The IBDV capsid protein fused to influenza virus peptides formed assemblies able to protect mice against viral challenge. Our studies establish the basis for a new generation of multivalent IBDV-based vaccines.

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“…Fully replicative FAdVs have been used previously to deliver peptide vaccines against the VP2 outer capsid antigen of IBDV (Sheppard et al, 1998;Francois et al, 2004). This approach relies on inducing an antibody-based response to IBDV.…”

Section: Discussionmentioning

confidence: 99%

“…In poultry, fowl adenovirus (FAdV) has been used to express a number of complex viral antigens (Sheppard et al, 1998;Johnson et al, 2003;Francois et al, 2004) and eukaryotic proteins including chicken interferon-g (Rauw et al, 2007), interleukin-2 (Cherenova et al, 2004) and thymidine kinase (Shashkova et al, 2005). These reports suggest that FAdV could be used as an effective delivery vector for complex eukaryotic proteins such as antibody fragments, with the added potential for prolonged in vivo release due to the replicative ability of the virus.…”

Section: Introductionmentioning

confidence: 99%

Antibody fragments, expressed by a fowl adenovirus vector, are able to neutralize infectious bursal disease virus

et al. 2010

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Single-chain variable fragments (scFv) contain the heavy and light chain variable domains of immunoglobulin, joined by a short peptide linker. Previously, our laboratory has produced neutralizing scFv to epitopes of infectious bursal disease virus (IBDV). The in vitro delivery and expression of one of these scFv with and without the C H 2-C H 4 Fc domain of chicken IgY attached (scFv-Fc) by a serotype 8 fowl adenovirus (FAdV-8) vector was investigated in the present study. A panel of FAdV-8 vectors was constructed, each containing a different transgene (scFv or scFv-Fc), a different promoter to drive scFv and scFv-Fc transcription (CMVie or the fowl adenovirus major late promoter), and a different sized, right-hand end genomic deletion (52 bp or 2.3 kb). This panel was used to establish what effect these variables had on protein production, viral replication and scFv transcription, as measured by enzyme-linked imunosorbent assay and real-time polymerase chain reaction. Our results showed that, using a FAdV-8 vector containing the optimal CMVie promoter/2.3 kb deletion combination, we successfully expressed a secreted form of both scFv and scFv-Fc that were able to neutralize IBDV both in vitro and in ovo. These studies indicate that the FAdV-8 vector may be a promising candidate to deliver and express therapeutic molecules such as scFv and scFv-Fc in vivo in poultry.

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Avian adenovirus CELO recombinants expressing VP2 of infectious bursal disease virus induce protection against bursal disease in chickens

Cited by 69 publications

References 32 publications

Oral Inoculation of Chickens with a Candidate Fowl Adenovirus 9 Vector

Oral Inoculation of Chickens with a Candidate Fowl Adenovirus 9 Vector

Structural Basis for the Development of Avian Virus Capsids That Display Influenza Virus Proteins and Induce Protective Immunity

Antibody fragments, expressed by a fowl adenovirus vector, are able to neutralize infectious bursal disease virus

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