Plant-produced chimeric virus-like particles – a new generation vaccine against African horse sickness.
Abstract: African horse sickness (AHS) is a severe arthropod-borne viral disease of equids, with a mortality rate of up to 95% in susceptible naïve horses. Due to safety concerns with the current live, attenuated AHS vaccine, alternate safe and effective vaccination strategies such as virus-like particles (VLPs) are being investigated. Transient plant-based expression systems are a rapid and highly scalable means of producing such African horse sickness virus (AHSV) VLPs for vaccine purposes. Results: In this study, we demonstrated that transient co-expression of the four AHSV capsid proteins in agroinfiltrated Nicotiana benthamiana dXT/FT plants not only allowed for the assembly of homogenous AHSV-1 VLPs but also single, double and triple chimeric VLPs, where one capsid protein originated from one AHS serotype and at least one other capsid protein originated from another AHS serotype. Following optimisation of a large scale VLP purification procedure, the safety and immunogenicity of the plant-produced, triple chimeric AHSV-6 VLPs was confirmed in horses, the target species. Conclusions: We have successfully shown assembly of single and double chimeric AHSV-7 VLPs, as well as triple chimeric AHSV-6 VLPs, in Nicotiana benthamiana dXT/FT plants. Plant produced chimeric AHSV-6 VLPs were found to be safe for administration into 6 month old foals as well as capable of eliciting a weak neutralizing humoral immune response in these target animals against homologous AHSV virus.
Publication Date: 2019-12-03 PubMed ID: 31796116PubMed Central: PMC6892175DOI: 10.1186/s12917-019-2184-2Google Scholar: Lookup
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Summary
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The research article focuses on the development of a new vaccination strategy against African Horse Sickness (AHS) by creating chimeric virus-like particles (VLPs) using plant-based expression systems. The authors have successfully demonstrated the assembly of these VLPs in agroinfiltrated Nicotiana benthamiana plants and confirmed their safety and immunogenicity in horses.
Background and Aim
- AHS is a severe viral disease affecting horses and is transmitted through arthropods. In susceptible horses, it has a mortality rate of up to 95%.
- Existing vaccines are live and attenuated but pose safety concerns. Therefore, this research aims to find an alternative method of vaccination that is safe and effective.
- The alternative vaccination strategy proposed in this research involves creating VLPs which are structurally similar to real viruses but non-infectious.
Methodology
- The researchers use a plant-based expression system, Nicotiana benthamiana, to produce the AHSV VLPs. The use of this plant allows for rapid production on a large scale.
- Four AHSV capsid proteins are co-expressed in the plant, resulting in the creation of various chimeric VLPs. These VLPs consist of one capsid protein from one AHS serotype and at least one other capsid protein from another serotype.
- An optimisation procedure for large-scale VLP purification is established to ensure that the particles are safe for administration.
Results and Conclusion
- The researchers managed to successfully assemble single, double, and triple chimeric VLPs in the Nicotiana benthamiana plants, demonstrating the viability of the approach.
- Trials on young horses showed the VLPs to be safe and capable of eliciting a weak neutralizing humoral immune response against the homologous AHSV virus. This suggests their potential use as a vaccine.
- In conclusion, the study showed that plant-produced, chimeric AHSV VLPs could be a viable alternative to existing AHS vaccines and serve as a new generation vaccine against the disease.
Cite This Article
APA
Rutkowska DA, Mokoena NB, Tsekoa TL, Dibakwane VS, O'Kennedy MM.
(2019).
Plant-produced chimeric virus-like particles – a new generation vaccine against African horse sickness.
BMC Vet Res, 15(1), 432.
https://doi.org/10.1186/s12917-019-2184-2 Publication
Researcher Affiliations
- CSIR Chemicals, PO Box 395, Pretoria, 0001, South Africa. DRutkowska@csir.co.za.
- Onderstepoort Biological Products SOC Ltd, Private Bag X07, Onderstepoort, 0110, South Africa.
- CSIR Chemicals, PO Box 395, Pretoria, 0001, South Africa.
- Onderstepoort Biological Products SOC Ltd, Private Bag X07, Onderstepoort, 0110, South Africa.
- CSIR Chemicals, PO Box 395, Pretoria, 0001, South Africa.
MeSH Terms
- African Horse Sickness / prevention & control
- African Horse Sickness Virus / immunology
- Animals
- Antibodies, Neutralizing / immunology
- Capsid Proteins / immunology
- Capsid Proteins / metabolism
- Gene Expression Regulation, Plant
- Horses
- Plants, Genetically Modified
- Recombinant Fusion Proteins
- Recombinant Proteins
- Nicotiana / metabolism
- Vaccines, Attenuated
- Vaccines, Virus-Like Particle
- Viral Vaccines
Grant Funding
- TAHC12 00013 / Technology and Innovation agency
Conflict of Interest Statement
DAR, NBM and MMOK have filed a patent application protecting the production of chimeric Orbivirus virus-like particles in plants (PCT/IB2017/052236).
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