Synthesis of recombinant baculoviruses expressing the outer capsid protein VP2 of five BTV serotypes and the induction of neutralizing antibodies to homologous and heterologous BTV serotypes

Urakawa, T; French, T J; Adachi, Yuchi; Fukusho, Akio; Leblois, H.; Flamand, Marie; Mertens, Peter P. C.; Roy, Polly

doi:10.1016/0168-1702(94)90001-9

Cited by 18 publications

(5 citation statements)

References 18 publications

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“…Experimental protein based BT vaccines all include the serotype specific immunodominant VP2 protein (Figure 3B). Protein production has been studied in bacteria (104), in insect cells (105–108), in yeast (109), and in plants (110–112).…”

Section: Vaccinesmentioning

confidence: 99%

Prospects of Next-Generation Vaccines for Bluetongue

Rijn

Piet²

2019

Front. Vet. Sci.

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Bluetongue (BT) is a haemorrhagic disease of wild and domestic ruminants with a huge economic worldwide impact on livestock. The disease is caused by BT-virus transmitted by Culicoides biting midges and disease control without vaccination is hardly possible. Vaccination is the most feasible and cost-effective way to minimize economic losses. Marketed BT vaccines are successfully used in different parts of the world. Inactivated BT vaccines are efficacious and safe but relatively expensive, whereas live-attenuated vaccines are efficacious and cheap but are unsafe because of under-attenuation, onward spread, reversion to virulence, and reassortment events. Both manufactured BT vaccines do not enable differentiating infected from vaccinated animals (DIVA) and protection is limited to the respective serotype. The ideal BT vaccine is a licensed, affordable, completely safe DIVA vaccine, that induces quick, lifelong, broad protection in all susceptible ruminant species. Promising vaccine candidates show improvement for one or more of these main vaccine standards. BTV protein vaccines and viral vector vaccines have DIVA potential depending on the selected BTV antigens, but are less effective and likely more costly per protected animal than current vaccines. Several vaccine platforms based on replicating BTV are applied for many serotypes by exchange of serotype dominant outer shell proteins. These platforms based on one BTV backbone result in attenuation or abortive virus replication and prevent disease by and spread of vaccine virus as well as reversion to virulence. These replicating BT vaccines induce humoral and T-cell mediated immune responses to all viral proteins except to one, which could enable DIVA tests. Most of these replicating vaccines can be produced similarly as currently marketed BT vaccines. All replicating vaccine platforms developed by reverse genetics are classified as genetic modified organisms. This implies extensive and expensive safety trails in target ruminant species, and acceptance by the community could be hindered. Nonetheless, several experimental BT vaccines show very promising improvements and could compete with marketed vaccines regarding their vaccine profile, but none of these next generation BT vaccines have been licensed yet.

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Section: Vaccinesmentioning

confidence: 99%

Prospects of Next-Generation Vaccines for Bluetongue

Rijn

Piet²

2019

Front. Vet. Sci.

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“…Immunologically, VP2 is the most important BTV protein [54–58], and inocula consisting of VP2 on its own or combined with VP5 have been tested as possible vaccine candidates, with variable results [11, 59]. Even though VP2 subunit vaccines provided protection at lower doses, no neutralising antibodies were detected after vaccination.…”

Section: Discussionmentioning

confidence: 99%

Development of plant-produced protein body vaccine candidates for bluetongue virus

2017

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BackgroundBluetongue is a disease of domestic and wild ruminants caused by bluetongue virus serotypes (BTV), which have caused serious outbreaks worldwide. Commercially available vaccines are live-attenuated or inactivated virus strains: these are effective, but there is the risk of reversion to virulence or reassortment with circulating strains for live virus, and residual live virus for the inactivated vaccines. The live-attenuated virus vaccines are not able to distinguish naturally infected animals from vaccinated animals (DIVA compliant). Recombinant vaccines are preferable to minimize the risks associated with these vaccines, and would also enable the development of candidate vaccines that are DIVA-compliant.ResultsIn this study, two novel protein body (PB) plant-produced vaccines were developed, Zera®-VP2ep and Zera®-VP2. Zera®-VP2ep contained B-cell epitope sequences of multiple BTV serotypes and Zera®-VP2 contained the full-length BTV-8 VP2 codon-optimised sequence. In addition to fulfilling the DIVA requirement, Zera®-VP2ep was aimed at being multivalent with the ability to stimulate an immune response to several BTV serotypes. Both these candidate vaccines were successfully made in N. benthamiana via transient Agrobacterium-mediated expression, and in situ TEM analysis showed that the expressed proteins accumulated within the cytoplasm of plant cells in dense membrane-defined PBs. The peptide sequences included in Zera®-VP2ep contained epitopes that bound antibodies produced against native VP2. Preliminary murine immunogenicity studies showed that the PB vaccine candidates elicited anti-VP2 immune responses in mice without the use of adjuvant.ConclusionsThese proof of concept results demonstrate that Zera®-VP2ep and Zera®-VP2 have potential as BTV vaccines and their development should be further investigated.Electronic supplementary materialThe online version of this article (doi:10.1186/s12896-017-0370-5) contains supplementary material, which is available to authorized users.

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“…Recombinant BTV protein vaccines include BTV subunit proteins expressed by different systems (insect cells [110,111], plant [112], yeast [113]); or bluetongue virus-like particles [114] that consist of the BTV capsid proteins expressed without the virus genetic material. Recombinant BTV protein vaccines can elicit immune responses in ruminants and even provide protection [115][116][117].…”

Section: Btv Vaccines: Live Attenuated Inactivated or Recombinant Vaccines?mentioning

confidence: 99%

Vaccination as a Strategy to Prevent Bluetongue Virus Vertical Transmission

2021

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Bluetongue virus (BTV) produces an economically important disease in ruminants of compulsory notification to the OIE. BTV is typically transmitted by the bite of Culicoides spp., however, some BTV strains can be transmitted vertically, and this is associated with fetus malformations and abortions. The viral factors associated with the virus potency to cross the placental barrier are not well defined. The potency of vertical transmission is retained and sometimes even increased in live attenuated BTV vaccine strains. Because BTV possesses a segmented genome, the possibility of reassortment of vaccination strains with wild-type virus could even favor the transmission of this phenotype. In the present review, we will describe the non-vector-based BTV infection routes and discuss the experimental vaccination strategies that offer advantages over this drawback of some live attenuated BTV vaccines.

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Synthesis of recombinant baculoviruses expressing the outer capsid protein VP2 of five BTV serotypes and the induction of neutralizing antibodies to homologous and heterologous BTV serotypes

Cited by 18 publications

References 18 publications

Prospects of Next-Generation Vaccines for Bluetongue

Prospects of Next-Generation Vaccines for Bluetongue

Development of plant-produced protein body vaccine candidates for bluetongue virus

Vaccination as a Strategy to Prevent Bluetongue Virus Vertical Transmission

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