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Plant-produced chimeric virus-like particles - a new generation vaccine against African horse sickness.

ABSTRACT: BACKGROUND: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.

SUBMITTER: Rutkowska DA

PROVIDER: S-EPMC6892175 | biostudies-literature | 2019 Dec

REPOSITORIES: biostudies-literature

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Plant-produced chimeric virus-like particles - a new generation vaccine against African horse sickness.

Rutkowska Daria A DA Mokoena Nobalanda B NB Tsekoa Tsepo L TL Dibakwane Vusi S VS O'Kennedy Martha M MM

BMC veterinary research 20191203 1

<h4>Background</h4>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 pur ...[more]

PMID: 31796116

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Project description:BACKGROUND:African horse sickness (AHS) is a serious viral disease of equids resulting in the deaths of many equids in sub-Saharan Africa that has been recognized for centuries. This has significant economic impact on the horse industry, despite the good husbandry practices. Currently, prevention and control of the disease is based on administration of live attenuated vaccines and control of the arthropod vectors. RESULTS:A total of 29 horses in 2 groups, were vaccinated. Eighteen horses in Group 1 were further divided into 9 subgroups of 2 horses each, were individually immunised with one of 1 to 9 AHS serotypes, respectively. The eleven horses of Group 2 were immunised with all 9 serotypes simultaneously with 2 different vaccinations containing 5 serotypes (1, 4, 7-9) and 4 serotypes (2, 3, 5, 6) respectively. The duration of this study was 12?months. Blood samples were periodically withdrawn for serum antibody tests using ELISA and VNT and for 2?weeks after each vaccination for PCR and virus isolation. After the booster vaccination, these 27 horses seroconverted, however 2 horses responded poorly as measured by ELISA. In Group 1 ELISA and VN antibodies declined between 5 to 7?months post vaccination (pv). Twelve months later, the antibody levels in most of the horses decreased to the seronegative range until the annual booster where all horses again seroconverted strongly. In Group 2, ELISA antibodies were positive after the first booster and VN antibodies started to appear for some serotypes after primary vaccination. After booster vaccination, VN antibodies increased in a different pattern for each serotype. Antibodies remained high for 12?months and increased strongly after the annual booster in 78% of the horses. PCR and virus isolation results remained negative. CONCLUSIONS:Horses vaccinated with single serotypes need a booster after 6?months and simultaneously immunised horses after 12?months. Due to the non-availability of a facility in the UAE, no challenge infection could be carried out.

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Plant-produced chimeric virus-like particles - a new generation vaccine against African horse sickness.

Publications

Plant-produced chimeric virus-like particles - a new generation vaccine against African horse sickness.

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