African horse sickness (AHS) is caused by multiple serotypes of the dsRNA AHSV and is a major scourge of domestic equids in Africa. While there are well established commercial live attenuated vaccines produced in South Africa, risks associated with these have encouraged attempts to develop new and safer recombinant vaccines. Previously, we reported on the immunogenicity of a plant-produced AHS serotype 5 virus-like particle (VLP) vaccine, which stimulated high titres of AHS serotype 5-specific neutralizing antibodies in guinea pigs. Here, we report a similar response to the vaccine in horses. This is the first report demonstrating the safety and immunogenicity of plant-produced AHS VLPs in horses.
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.
17 May 2023 in Proceedings of the ACM on Human-Computer Interaction
The paper contributes to scanpath bundling methods. We propose an analytical approach for statistical comparisons of aggregated scanpath visualizations by means of second-order gaze analysis metrics. The present study explores differences in attention distribution and cognitive processing over architectural objects between architects, art historians, and non-experts. The results show between-group differences in attention dynamics of the aggregated scanpaths. The aggregated scanpaths of both expert groups were focal, while non-experts' scanpaths were ambient. Experts also paid more attention to and tended to remember better the architectural details and their location. The discussion explores the scalability of the proposed approach for Human-Computer Interaction and accessibility technologies designed to enhance the experience of cultural heritage.
Brucellosis is an important bacterial disease of livestock and the most common zoonotic disease. The current vaccines are effective but unsafe, as they result in animal abortions and are pathogenic to humans. Virus-like particles are being investigated as molecular scaffolds for foreign antigen presentation to the immune system. Here, we sought to develop a new-generation vaccine by presenting selected Brucella melitensis T cell epitopes on the surface of Orbivirus core-like particles (CLPs) and transiently expressing these chimeric particles in Nicotiana benthamiana plants. We successfully demonstrated the assembly of five chimeric CLPs in N. benthamiana plants, with each CLP presenting a different T cell epitope. The safety and protective efficacy of three of the highest-yielding CLPs was investigated in a mouse model of brucellosis. All three plant-expressed chimeric CLPs were safe when inoculated into BALB/c mice at specific antigen doses. However, only one chimeric CLP induced protection against the virulent Brucella strain challenge equivalent to the protection induced by the commercial Rev1 vaccine. Here, we have successfully shown the assembly, safety and protective efficacy of plant-expressed chimeric CLPs presenting B. melitensis T cell epitopes. This is the first step in the development of a safe and efficacious subunit vaccine against brucellosis.
Cancer is a major global health problem that poses significant challenges. Conventional cancer therapies often have severe side effects, necessitating the development of novel therapeutic approaches that are more effective and less toxic. The utilization of plant viral nanoparticles is one of the more promising strategies for cancer biotherapy. Plant viral nanoparticles exhibit advantageous properties, including safety, high stability, rapid production and scalability, biocompatibility and biodegradability, structural uniformity, inherent immunogenicity, ease of modification and high update efficacy as well as lower cost implications, making them attractive vehicles for health applications. Various studies have demonstrated the efficacy of plant viral nanoparticles in targeted therapeutic drug/molecule delivery, tumor imaging and immunotherapy, highlighting their potential as a versatile platform for cancer biotherapy. The drawbacks of plant viral nanoparticles include their perceived ability to induce a hypersensitive/allergic immune response, non-well-defined regulatory approval processes as well as the reluctance of pharmaceutical companies to adapt their manufacturing processes to facilitate plant-based expression. This review discusses applications of plant virus-derived nanoparticles in cancer therapeutics and prospects for translating these findings into clinical practice.