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

Abstract

BackgroundAfrican 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.ResultsIn 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.ConclusionsWe 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.

Plant-Derived Recombinant Vaccines against Zoonotic Viruses

“…The virus-like particles can be formed from structural proteins belonging to one type or multiple types of viruses. Those composed of structural proteins or immunogenic epitopes from different viruses are known as chimeric VLPs [54][55][56][57]. Such VLPs can be used as immune modulators and self-adjuvants to provoke strong immune responses against the presented immunogenic epitopes [58][59][60].…”

African horse sickness in Thailand: Challenges of controlling an outbreak by vaccination

“…Indeed, these new vaccines use selected viral protective antigen(s) enabling the development of complementary diagnostic tests based on the antigen and gene segments that are not included in the vaccine. The DISA (Disabled Infectious Single Animal), 20 DISC (Disabled Infectious Single Cycle), 21 VLP (virus‐like particle) 22‐24 approaches are all attractive options for further research and are theoretically DIVA compatible. Their disadvantage for DIVA is that on top of developing the vaccine, investment is needed to develop and validate the DIVA accompanying test.…”

Reverse genetics approaches: a novel strategy for African horse sickness virus vaccine design

“…Of concern, LAVs are associated with reversion to virulence, vector’s transmission, absence of DIVA (Differentiating Infected from Vaccinated Animals) capacity, teratogenicity, and gene reassortment that lead to the establishment of new genetic variants [ 3 , 14 , 15 , 16 , 17 , 18 ]. To address the need for safe and more effective vaccines, several candidates have been evaluated including subunit vaccines, virus like particles (VLPs), avian reovirus muNS protein microspheres (MS), recombinant poxviruses and reverse genetic approaches [ 19 , 20 , 21 , 22 , 23 , 24 , 25 , 26 , 27 , 28 •• , 29 •• , 30 , 31 , 32 , 33 , 34 , 35 , 36 , 37 • ] ( Table 1 ).…”

“…A multiserotype cocktail of subunit VP2 vaccine (serotypes 2, 4, 5, 6, 9) was tested in guinea pigs eliciting a low cross-neutralizing antibody response for genetically related AHSV-8 [ 32 ]. In addition, recombinant baculovirus expression systems that allowed the assembly of VLPs have been reported [ 33 , 34 , 35 , 36 ]. Currently, transient expression in plants is being used for a relatively easy production of VLPs.…”

“…Sera from horses immunized with AHSV-5 VLPs also elicited similar antibody titres towards AHSV-8. In further studies, plant-produced triple chimeric AHSV-1/AHSV-3/AHSV-6 VLPs, composed of a combination of capsid proteins, induced moderate NAbs titres against AHSV-6 in horses [ 34 ].…”