Validation of a novel approach for the rapid production of immunogenic virus-like particles for bluetongue virus

Stewart, Meredith; Bhatia, Yeshika; Athmaran, T N; Noad, Rob; Gastaldi, Cristina; Dubois, Éric; Russo, Pierre; Thiéry, Richard; Sailleau, Corinne; Bréard, Emmanuel; Zientara, Stéphan; Roy, Polly

doi:10.1016/j.vaccine.2009.10.072

Cited by 45 publications

(33 citation statements)

References 35 publications

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“…Thus, a variety of alternate approaches have been undertaken to generate BTV vaccines, many of which have been tested in laboratory conditions with some level of success (1,13,14,21,30,32). In fact, our laboratory has demonstrated strong evidence supporting the VLPs as a good alternative to current vaccines (9,28,30,32,33). A completely different strategy, such as defective viruses which could trigger protective immune responses but do not replicate in vaccinated animals, has not been possible to develop due to the lack of a reverse genetics system for BTV in the past.…”

Section: Discussionmentioning

confidence: 99%

“…Early vaccines against BTV were attenuated virus strains; however, the use of these vaccines to control the disease has had a number of unwanted consequences, including teratological effects in newborn animals when pregnant sheep and cattle were vaccinated and reversion of the vaccine strains or reassortment between vaccine and field strains, leading to the generation of virulent strains (11,20,29). The serotype determinant for the virus (VP2) has been shown to be protective in sheep, as have virus-like particles (VLPs) produced by coexpression of the four structural proteins of the viral capsid (9,30,33). However, no commercial recombinant subunit BTV vaccine is currently available.…”

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confidence: 99%

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Generation of Replication-Defective Virus-Based Vaccines That Confer Full Protection in Sheep against Virulent Bluetongue Virus Challenge

Matsuo

Celma

Boyce

et al. 2011

J Virol

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The reverse genetics technology for bluetongue virus (BTV) has been used in combination with complementing cell lines to recover defective BTV-1 mutants. To generate a potential disabled infectious single cycle (DISC) vaccine strain, we used a reverse genetics system to rescue defective virus strains with large deletions in an essential BTV gene that encodes the VP6 protein (segment S9) of the internal core. Four VP6-deficient BTV-1 mutants were generated by using a complementing cell line that provided the VP6 protein in trans. Characterization of the growth properties of mutant viruses showed that each mutant has the necessary characteristics for a potential vaccine strain: (i) viral protein expression in noncomplementing mammalian cells, (ii) no infectious virus generated in noncomplementing cells, and (iii) efficient replication in the complementing VP6 cell line. Further, a defective BTV-8 strain was made by reassorting the two RNA segments that encode the two outer capsid proteins (VP2 and VP5) of a highly pathogenic BTV-8 with the remaining eight RNA segments of one of the BTV-1 DISC viruses. The protective capabilities of BTV-1 and BTV-8 DISC viruses were assessed in sheep by challenge with specific virulent strains using several assay systems. The data obtained from these studies demonstrated that the DISC viruses are highly protective and could offer a promising alternative to the currently available attenuated and killed virus vaccines and are also compliant as DIVA (differentiating infected from vaccinated animals) vaccines.

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Section: Discussionmentioning

confidence: 99%

mentioning

confidence: 99%

Generation of Replication-Defective Virus-Based Vaccines That Confer Full Protection in Sheep against Virulent Bluetongue Virus Challenge

Matsuo

Celma

Boyce

et al. 2011

J Virol

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“…These attributes render VLPs safer than the conventional vaccines and superior to recombi-nant single-protein subunit vaccines in eliciting strong, long-lived protective immune responses, even in the absence of adjuvants (Noad and Roy, 2003;Grgaciac and Anderson, 2006). Notably, VLPs of the prototype orbivirus, bluetongue virus (BTV), produced by baculovirus-mediated co-expression of the four major structural proteins (VP2, VP5, VP7 and VP3) in insect cells, were shown to stimulate a long-lasting protective immune response in vaccinated sheep Stewart et al, 2010).…”

Section: Introductionmentioning

confidence: 99%

Synthesis of empty african horse sickness virus particles

Maree

Putterill

et al. 2016

Virus Research

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As a means to develop African horse sickness (AHS) vaccines that are safe and DIVA compliant, we investigated the synthesis of empty African horse sickness virus (AHSV) particles. The emphasis of this study was on the assembly of the major viral core (VP3 and VP7) and outer capsid proteins (VP2 and VP5) into architecturally complex, heteromultimeric nanosized particles. The production of fully assembled corelike particles (CLPs) was accomplished in vivo by baculovirus-mediated co-synthesis of VP3 and VP7. The two different outer capsid proteins were capable of associating independently of each other with preformed cores to yield partial virus-like particles (VLPs). Complete VLPs were synthesized, albeit with a low yield. Crystalline formation of AHSV VP7 trimers is thought to impede high-level CLP production. Consequently, we engineered and co-synthesized VP3 with a more hydrophilic mutant VP7, resulting in an increase in the turnover of CLPs.

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“…Assuming that VP2 plays the primary role in protection, these results imply that 25-50 fold less VP2 is sufficient for protection if presented by VLPs, compared with VP2 or VP2/ VP5 subunit vaccines (Roy et al, 1992). Later, multiple gene baculovirus expression vectors have been used, which express all four BT capsid proteins by one baculovirus leading to more efficient VLP production (Belyaev and Roy, 1993;Stewart et al, 2010). VLPs have been generated for multiple serotypes and cocktails of serotypes 1, 2, 10, 13, and 17 have been tested.…”

Section: Virus-like Particlesmentioning

confidence: 99%

Current and next-generation bluetongue vaccines: Requirements, strategies, and prospects for different field situations

Feenstra

Rijn

2016

Critical Reviews in Microbiology

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Validation of a novel approach for the rapid production of immunogenic virus-like particles for bluetongue virus

Cited by 45 publications

References 35 publications

Generation of Replication-Defective Virus-Based Vaccines That Confer Full Protection in Sheep against Virulent Bluetongue Virus Challenge

Generation of Replication-Defective Virus-Based Vaccines That Confer Full Protection in Sheep against Virulent Bluetongue Virus Challenge

Synthesis of empty african horse sickness virus particles

Current and next-generation bluetongue vaccines: Requirements, strategies, and prospects for different field situations

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