Infectious bursal disease subviral particles displaying the foot-and-mouth disease virus major antigenic site

Remond, Michèle; Costa, Bruno Da; Sabine, Riffault; Parida, Satya; Bréard, Emmanuel; Lebreton, Françoise; Zientara, Stéphan; Delmas, Bernard

doi:10.1016/j.vaccine.2008.10.036

Cited by 20 publications

(15 citation statements)

References 24 publications

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“…Structural constraints are unclear and must be established empirically; in our system, VLP assembly is impeded in VP2 chimeras with M2 or HA2 inserted into the P HI loop (which does not contribute to intratrimeric interactions), whereas the P BC loop incorporated a 12-amino-acid FMDV epitope in Tϭ1 SVPs (29).…”

Section: Discussionmentioning

confidence: 99%

“…The Tϭ1 SVP platform nevertheless entails considerable space limitations, as its cargo space is only 380 nm 3 . Exposed loops at the tip of the trimeric VP2 spikes could be alternative targets for heterologous peptide insertion (28), such as the P BC loop (between ␤ strands B and C of the P domain) that incorporates foot-and-mouth disease virus (FMDV) epitopes in Tϭ1 SVPs (29).…”

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confidence: 99%

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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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Section: Discussionmentioning

confidence: 99%

mentioning

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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“…26,27 Some viral coat proteins assemble spontaneously either into virus-like particles (VLPs), which have the same size and morphology as the parent virus, or into subviral particles (SVPs), which differ from the parent virus in size and structure often because the parent virus comprises several different CP subunits whereas SVPs are homomeric. 28–32 …”

Section: Introductionmentioning

confidence: 99%

A potential nanobiotechnology platform based on infectious bursal disease subviral particles

et al. 2012

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We describe a novel nanobiotechnology platform based on subviral particles derived from infectious bursal disease virus (IBD-SVPs). The major virus coat protein VP2 assembles into spherical, 23 nm SVPs when expressed as a heterologous protein in the yeast Pichia pastoris. We recovered up to 38 mg of IBD-SVPs at > 95% purity from 1 L of recombinant yeast culture. The purified particles were able to tolerate organic solvents up to 20% concentration (ethanol or dimethylsulfoxide), they resisted temperatures up to 65 °C and remained stable over a wide pH range (2.5–9.0). We achieved bioconjugation to the amine groups of lysine residues and to the carboxyl groups of aspartic and glutamic acid residues, allowing the functionalization of IBD-SVPs with biotin. The accessibility of surface amine groups was measured using Alexa Fluor 488 N-hydroxysuccinimide (NHS) ester, an amine-selective fluorescent dye, revealing that approximately 60 dye molecules were attached to the surface of each particle. IBD-SVPs can therefore be exploited as a robust and versatile nanoscaffold to display diverse functional ligands.

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“…In this way, several chimeric VLPs have been developed carrying heterologous sequences in rotavirus backbones [11], Hepatitis B core and e antigens [13] as well as porcine parvovirus [14,15]. However, in most of the studies the size of the heterologous insertions was limited to 15-25 amino acids, which restricts the use of VLPs as carriers [16,17]. Unfortunately, in some cases the immunodominant epitope of a protein is not certainly known, especially mainly regarding the development of cellular responses.…”

Section: Introductionmentioning

confidence: 99%

Double-layered rotavirus-like particles are efficient carriers to elicit strong CTL responses to delivered heterologous antigens

Molinari

Peralta

Maletto

et al. 2014

Process Biochemistry

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Infectious bursal disease subviral particles displaying the foot-and-mouth disease virus major antigenic site

Cited by 20 publications

References 24 publications

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

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

A potential nanobiotechnology platform based on infectious bursal disease subviral particles

Double-layered rotavirus-like particles are efficient carriers to elicit strong CTL responses to delivered heterologous antigens

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