Safety and immunogenicity of plant-produced African horse sickness virus-like particles in horses

Dennis, Susan J.; O’Kennedy, Martha M.; Rutkowska, Daria; Tsekoa, Tsepo L.; Lourens, Carina W.; Hitzeroth, Inga I.; Meyers, Ann E.; Rybicki, Edward P.

doi:10.1186/s13567-018-0600-4

Cited by 31 publications

(25 citation statements)

References 15 publications

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“…Consequently, the widespread use of such attenuated vaccines against BT was not recommended, and the recent BTV outbreak in Europe was controlled using inactivated vaccines [21,22]. This led to the use of inactivated AHS vaccines [17] and the development of novel vaccines such as subunit vaccines and plant-based vaccines [28][29][30], thus avoiding these potential drawbacks. RNA fragments encoding the structural proteins VP2 and VP5 in the outer AHSV capsid, which are responsible for neutralising antibody production, can be inserted into different viruses, such as Baculovirus, vaccinia virus or capripox virus.…”

Section: Discussionmentioning

confidence: 99%

Immune response of horses to inactivated African horse sickness vaccines

et al. 2020

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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 Blood samples were periodically withdrawn for serum antibody tests using ELISA and VNT and for 2 weeks after each vaccination for PCR and virus isolation.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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Section: Discussionmentioning

confidence: 99%

Immune response of horses to inactivated African horse sickness vaccines

et al. 2020

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“…This led to the use of inactivated AHS vaccines (17) and the development of novel vaccines such as subunit vaccines and plant-based vaccines (29,30,31), thus avoiding these potential drawbacks. RNA fragments encoding the structural proteins VP2 and VP5 in the outer AHSV capsid, which are responsible for neutralising antibody production, can be inserted into different viruses, such as Baculovirus, vaccinia virus or capripox virus.…”

Section: Discussionmentioning

confidence: 99%

Immune response of horses to inactivated African horse sickness vaccines

Rodrı́guez

Joseph

Pfeffer

et al. 2020

Preprint

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Background: African horse sickness (AHS) is a devastating disease of equids that has been known for centuries. Many equids mainly in sub-Saharan Africa still die every year from this viral disease. This has an enormous economic impact on the horse industry, notwithstanding the dedication of horse owners in the daily care of their animals. Currently, prevention and control of the disease are based on live attenuated vaccines and control vector arthropods.Results: A total of 29 horses kept in an isolated desert area were divided into 2 groups and subcutaneously (sc) vaccinated. In Group 1, a total of 18 horses divided into 9 subgroups of 2 horses each were individually immunised with AHS serotypes 1 to 9. Eleven horses in Group 2 were immunised with all 9 serotypes simultaneously with 2 different injections by the combination of vaccine 1 containing 5 serotypes (1, 4, 7, 8, 9) and vaccine 2 containing 4 serotypes (2, 3, 5, 6). The vaccination experiment lasted 12 months. Blood samples were periodically drawn for serum antibody tests using ELISA and VNT. After each vaccination, blood was collected during a period of 2 weeks for PCR and virus isolation. After the booster vaccination, 27 horses seroconverted to the inactivated vaccines, but 2 horses responded poorly, as measured by ELISA. In Group 1, ELISA and VN antibodies declined between 5 and 7 months post vaccination (pv). Twelve months later, the antibody level in most of the horses dropped to the negative range, but after the annual booster, all horses again seroconverted strongly, as early as 1 week pv. In Group 2, ELISA antibodies turned positive after the first booster, and VN antibodies started to appear for some serotypes after primary vaccination. After the 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 were negative.Conclusions: Horses vaccinated with single serotypes need a booster after 6 months, while simultaneously immunised horses need one 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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“…One of the more exciting developments in molecular farming of animal virus vaccines in recent years was the demonstration that BTV serotype 8 VLPs—which contain four capsid proteins, and were previously only produced in insect cells (Roy, Bishop, LeBlois, & Erasmus, )—could be efficiently and reliably produced via Agrobacterium ‐mediated transient expression in N. benthamiana , and that these were as protective in sheep as the gold standard live attenuated virus vaccine (Thuenemann, Meyers, et al, ; van Zyl, Meyers, & Rybicki, ; Figure ). This success was subsequently replicated for the generically related African horse sickness orbiviruses (AHSVs) serotypes 4 and 5, where the VNPs were found to be stable, highly immunogenic, and to elicit neutralizing and cross‐neutralizing antibodies in horses (Dennis et al, ). This success was unexpected given the complexity of the particles and their assembly; however, it opens the way to make complete inert capsid‐based vaccines for all 25 bluetongue and all nine African horse sickness virus serotypes, as well as the economically important orbiviruses epizootic hemorrhagic disease virus and equine encephalosis virus, both viruses of horses.…”

Section: Animal Virus‐derived Vnpsmentioning

confidence: 95%

“…Transmission electron micrographs showing AHSV 5 VLPs made by transient Agrobacterium ‐mediated expression in Nicotiana benthamiana plants, and purified by discontinuous iodixanol density gradient ultracentrifugation (Dennis et al, ). Scale bar: 50–200 nm.…”

Section: Animal Virus‐derived Vnpsmentioning

confidence: 99%

Plant molecular farming of virus‐like nanoparticles as vaccines and reagents

Rybicki

2019

WIREs Nanomed Nanobiotechnol

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The use of plants for the production of virus‐like nanoparticles (VNPs) dates back to separating natural empty capsids of plant viruses from whole virions nearly 70 years ago, through to the present use of transgenic plants or recombinant Agrobacterium tumefaciens and/or plant virus‐derived vectors for the transient expression of engineered viral or other structural proteins in plants—a production system also known as molecular farming. Plant production of heterologous proteins has major advantages in terms of convenience—whole plants are generally used, and processes do not need to be sterile—and cost, as bulk biomass production is significantly cheaper than by any other method. Plant‐made VNPs in current use for nanotechnology include whole virions and naturally occurring empty capsids of plant viruses, and particles made by reassembly of coat protein (CP) purified from virions or by recombinant expression. Engineered VNP‐forming animal or human virus CPs expressed in plants include L1 protein from human papillomaviruses, human norovirus CP, hepatitis B surface and core antigens, influenza virus HA protein and HIV Gag polyprotein forming large enveloped particles by budding, orbi‐ and rotavirus particles that require assembly of four co‐expressed proteins, and polio‐ and foot and mouth disease viruses which require proteolytic processing of a polyprotein precursor to form 4‐component VNPs. Both plant and animal virus‐derived plant‐made VNPs can be used for surface and internal display of heterologous peptides or even whole proteins. A significant recent development has been the production of pseudovirions in plants, comprising plant or animal virus CPs and RNA or DNA pseudogenomes that can be used to deliver nucleic acid payloads into cultured cells or specific tissues or tumors in whole animals. This article is characterized under: Biology‐Inspired Nanomaterials > Protein and Virus‐Based Structures Therapeutic Approaches and Drug Discovery > Emerging Technologies Diagnostic Tools > in vivo Nanodiagnostics and Imaging

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Safety and immunogenicity of plant-produced African horse sickness virus-like particles in horses

Cited by 31 publications

References 15 publications

Immune response of horses to inactivated African horse sickness vaccines

Immune response of horses to inactivated African horse sickness vaccines

Immune response of horses to inactivated African horse sickness vaccines

Plant molecular farming of virus‐like nanoparticles as vaccines and reagents

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