A PhD candidate at the University of Cape Town developing a vaccine against African horse sickness
Production of a safe, efficacious and cost-effective alternative vaccine against AHS
AHSV is a devastating disease which has an enormous impact on the equestrian and farming community. The virus is responsible for great suffering and many horse deaths in South Africa. AHS-free countries with milder climate conditions are increasingly at risk for outbreaks of the disease due to the migration northwards of the Culicoides midge species. The live attenuated AHSV vaccine currently used in South Africa is not considered safe enough for licensed use in countries where the virus is not present, including the EU. This has a major negative impact on the equine industry and sport, due to strict international travel controls to and from endemic countries. In Southern Africa, many subsistence farmers depend on horses for carrying out their farming activities. Loss of horses due to this dreadful disease has a crippling effect on their productivity and the security of their livelihood. This in turn, has a ripple effect on the economy of the country. The development of a safe, efficacious and cost effective alternative AHSV vaccine should thus be given the highest priority. The spread of AHSV can be prevented by vaccination of animals, but the development of safe and effective vaccines has been difficult. Live attenuated vaccines have been in use for more than 5 decades but they have many shortcomings. Inactivated viral strains are expensive and require multiple doses and boosters for immunity to be maintained in animals. These concerns have motivated efforts to develop safer vaccines and one of the approaches has been the production of virus-like particles (VLPs) for use as vaccines. VLPs resemble the conformation of the native virus, but contain only the four structural proteins of AHSV. They are non-infectious and are unable to replicate as they do not contain the viral genetic material. Virus-like particles (VLPs) are excellent vaccine candidates, because there is no risk of reversion to virulence or re-assortment with wild virus strains, as they only contain structural proteins. Furthermore, particulate antigens like VLPs are likely to elicit a superior immune response due to certain key characteristics eg. the VLP surface displays a dense repetitive array of epitopes for presentation to the immune system. Another advantage of using VLP vaccines above live attenuated viral vaccines is that they would allow differentiation between vaccinated and infected animals as VLPs do not contain any of the non-structural proteins nor viral genetic material.
Abstract: African horse sickness virus (AHSV) is a lethal arbovirus of equids that is transmitted between hosts primarily by biting midges of the genus Culicoides (Diptera: Ceratopogonidae). AHSV affects draft, thoroughbred, and companion horses and donkeys in Africa, Asia, and Europe. In this review, we examine the impact of AHSV critically and discuss entomological studies that have been conducted to improve understanding of its epidemiology and control. The transmission of AHSV remains a major research focus and we critically review studies that have implicated both Culicoides and other blood-feeding arthropods in this process. We explore AHSV both as an epidemic pathogen and within its endemic range as a barrier to development, an area of interest that has been underrepresented in studies of the virus to date. By discussing AHSV transmission in the African republics of South Africa and Senegal, we provide a more balanced view of the virus as a threat to equids in a diverse range of settings, thus leading to a discussion of key areas in which our knowledge of transmission could be improved. The use of entomological data to detect, predict and control AHSV is also examined, including reference to existing studies carried out during unprecedented outbreaks of bluetongue virus in Europe, an arbovirus of wild and domestic ruminants also transmitted by Culicoides.
Pub.: 01 Feb '17, Pinned: 27 Jul '17
Abstract: Emerging viruses pose a major threat to humans and livestock with global public health and economic burdens. Vaccination remains an effective tool to reduce this threat, and yet, the conventional cell culture often fails to produce sufficient vaccine dose. As an alternative to cell-culture based vaccine, virus-like particles (VLPs) are considered as a highpriority vaccine strategy against emerging viruses. VLPs represent highly ordered repetitive structures via macromolecular assemblies of viral proteins. The particulate nature allows efficient uptake into antigen presenting cells stimulating both innate and adaptive immune responses towards enhanced vaccine efficacy. Increasing research activity and translation opportunity necessitate the advances in the design of VLPs and new bioprocessing modalities for efficient and cost-effective production. Herein, we describe major achievements and challenges in this endeavor, with respect to designing strategies to harnessing the immunogenic potential, production platforms, downstream processes, and some exemplary cases in developing VLP-based vaccines.
Pub.: 01 Mar '17, Pinned: 27 Jul '17
Abstract: African horse sickness (AHS) is a debilitating and often fatal viral disease affecting horses in much of Africa, caused by the dsRNA orbivirus African horse sickness virus (AHSV). Vaccination remains the single most effective weapon in combatting AHS, as there is no treatment for the disease apart from good animal husbandry. However, the only commercially available vaccine is a live attenuated version of the virus (LAV). The threat of outbreaks of the disease outside its endemic region and the fact that the LAV is not licensed for use elsewhere in the world, have spurred attempts to develop an alternative safer, yet cost-effective recombinant vaccine. Here we report the plant-based production of a virus-like particle (VLP) AHSV serotype 5 candidate vaccine by Agrobacterium tumefaciens-mediated transient expression of all four capsid proteins in Nicotiana benthamiana using the cowpea mosaic virus-based HyperTrans (CPMV-HT) and associated pEAQ plant expression vector system. The production process is fast and simple, scalable, economically viable, and most importantly, guinea pig antiserum raised against the vaccine was shown to neutralise live virus in cell-based assays. To our knowledge, this is the first report of AHSV VLPs produced in plants, which has important implications for the containment of, and fight against the spread of, this deadly disease. This article is protected by copyright. All rights reserved.
Pub.: 27 Jun '17, Pinned: 27 Jul '17
Abstract: African horse sickness (AHS) is a hemorrhagic viral fever of horses. It is the only equine disease for which the World Organization for Animal Health has introduced specific guidelines for member countries seeking official recognition of disease-free status. Since 1997, South Africa has maintained an AHS controlled area; however, sporadic outbreaks of AHS have occurred in this area. We compared the whole genome sequences of 39 AHS viruses (AHSVs) from field AHS cases to determine the source of 3 such outbreaks. Our analysis confirmed that individual outbreaks were caused by virulent revertants of AHSV type 1 live, attenuated vaccine (LAV) and reassortants with genome segments derived from AHSV types 1, 3, and 4 from a LAV used in South Africa. These findings show that despite effective protection of vaccinated horses, polyvalent LAV may, paradoxically, place susceptible horses at risk for AHS.
Pub.: 22 Jul '16, Pinned: 27 Jul '17