A new vaccine hope for African horse sickness, from an unlikely source
FOR IMMEDIATE RELEASE | 22 NOVEMBER 2018
Researchers at the University of Cape Town’s Biopharming Research Institute (BRU) have created a promising new vaccine candidate to help prevent the devastating effects of African Horse Sickness (AHS). And they’re producing it in tobacco plants.
“We’ve got a vaccine candidate that’s extremely immunogenic,” says Prof Ed Rybicki, Director of the BRU. “It also produces neutralising antibodies when administered to healthy horses.” That means that the vaccine works really well in initial tests, but needs to be tested against an actual outbreak of AHS before it can be sold. BRU recently published these results in the respected Veterinary Research journal.
The need for an effective AHS vaccine is pressing. The disease is a devastating one, particularly in Africa, with up to 90% of infected horses dying in some outbreaks. The current commercial vaccine is known as a live-attenuated vaccine, and while it remains effective, it carries some risks. According to Prof Alan Guthrie, Director of the Equine Research Centre at the University of Pretoria and a former collaborator on this project, live vaccines can and occasionally do cause outbreaks of their own.
“There are two problems with a live-attenuated virus vaccine – reassortment of the genome and reversion to virulence,” he says. “Both can lead to outbreaks, which is what happened in the Cape in three different AHS outbreaks over the last 15 years – in 2004, 2011, and 2014.”
This is why other parts of the world don’t use the currently-available vaccine, says Guthrie. And this is a looming threat, as a changing climate allows the midge that carries the virus to spread to new parts of Europe and the United Kingdom.
According to Sue Dennis, PhD candidate and lead author on this study, the BRU’s plant-produced vaccine doesn’t carry any of these risks, which makes it suitable for use around the world.
“We’ve used tobacco plants to produce four different virus proteins that automatically assemble to form a virus-like particle (VLP). It looks the same as the virus, just without any genetic material; so it cannot replicate or infect horses with the disease.”
This VLP is the vaccine – when injected into an animal, the immune system produces antibodies to the virus that will fend off the real thing and protect the animal from disease. Dennis says that initial results look very promising, but there is more work to be done.
“When we tested the plant-produced vaccine in healthy horses, we saw an immune response at the same level as the live vaccine,” she says. When first testing vaccines in live animals, the most important thing is to show that the animal’s health is not affected, and that the immune system produces neutralising antibodies – the best indication that the vaccine will work against the live virus. On both counts, the BRU study has been a success.
“The presence of neutralising antibodies is a strong indication that horses will be protected from the virus,” she says. “But to confirm that the vaccine offers complete protection, we need what’s called a live challenge.”
In addition, the VLPs produced by Dennis and colleagues represent just one strain of AHSV; they are currently working on producing vaccines against the other strains.
This success builds on more than 10 years of work at the BRU producing VLPs and other proteins in tobacco plants. In particular, years of work on bluetongue virus, which is related to AHS virus, has contributed to this breakthrough.
The next step is to test the protective power of the vaccine in horses against a challenge with live, virulent AHSV (the so-called live challenge), to see whether this promising vaccine candidate can stand up against the live virus. If it does as well as the current live-attenuated vaccine, BRU researchers believe they will be well on their way to a new global AHS vaccine.
This research was funded in part by the Technology Innovation Agency, and related intellectual property has been protected through UCT’s Department of Research, Contracts and Innovation, who receive a rebate from the DST National IP Management Office (NIPMO) to support patenting.
The Biopharming Research Unit (BRU, Department of Molecular and Cell Biology at UCT) makes recombinant proteins in plants for use as diagnostics or vaccines for human and animal diseases. The Unit comprises research groups led by Professor Ed Rybicki, Associate Professor Inga Hitzeroth and Dr Ann Meyers, and boasts the largest portfolio of biotechnology patents at UCT, as well as the largest molecular biotechnology portfolio in South Africa.
Research Contracts and Innovation (RC&I) acts as the liaison between UCT’s research community and the private sector with regards to intellectual property protection, commercialisation and business development activities.
I have had a Web presence since we first had access to the Web, here at the University of Cape Town, back in 1994: a few of us had discovered this new and shiny thing, and asked our IT Services if UCT had a server – to be told “Yes, but you can’t use it”. We – my colleague Vernon Coyne and I – quickly disabused them of this notion, and got unfettered access to what was then a very primitive Webiverse. Imagine: we were still using FTP and Gopher to move stuff around on the internet at the time; we also had to compose our self-taught HTML using Windows Notepad, for browsers like Cello that didn’t support graphics!
I pretty quickly got the notion that one could teach Virology via the Web, and set up teaching pages from 1995 or so that survived until UCT’s Big Clean Up a few years ago, which basically killed the whole legacy Web environment for us. Delightfully primitive they were, at first: I blogged about this here two years ago, noting that the ONLY record of all that work was via the Wayback server, that has an admirable if slightly spotty set of historical links to material that does not survive anywhere else.
Something that was potentially more valuable though, and which I pioneered at UCT from 1995, was the real-time updating of virological news – started in 1995 with the Ebola Zaire outbreak in Kikwit in the DRC, and commemorated here 20 years on. I was essentially compiling a daily digest of news on the Kikwit outbreak, and later also on others, and also on Marburg, via sources such as ProMed and internet discussion groups. It all started with an essay by my 1994 Honours student, Alison Jacobson, that was one of the first things I put up on the Web. This subsequently ended up being one of the only sources of information on the virus available online for a while, which terrified Alison, and which I commemorated here.
I used this material at the time to inform undergrad students in second-and third-year courses as to what was going on in the moment – and give them cutting-edge material for exam purposes even after my section(s) of their course(s) had finished.
Inevitably things changed and moved on, and I got busy doing other career-related things – then my long-time internet guru Alan Cann introduced me to the concept of regular blogging via WordPress, and slicker news aggregators such as Scoop.it, and Twitter. This is of course the blog site I set up in 2007 as a teaching blog for Virology after guesting on his MicrobiologyBytes site a number of times – and I see with some sadness that his site no longer exists. I did things with ViroBlogy like blogging in detail in 2008 on a great paper describing single-round replication of a West Nile virus vaccine candidate – and then asking a detailed question on it in the 3rd year Defence and Disease course exam, despite there being no coverage of it during the course.
I also signed up for Twitter as @edrybicki in 2008 – mainly to tweet about cups of coffee and Marmite-coated biscuits, it would seem, although I see H1N1pdm flu getting to South Africa got a mention.
I then started up Virology News in 2012 on the Scoop.it site, again following The Guru Cann, for disseminating a wider, more general set of news about viruses to a wider audience. Oh, and news about zombies. And sometimes Led Zeppelin too B-)
Scoop.it actually turned out to be an excellent add-on to my existing sites, as it could be set up to automatically tweet anything I put up in it, or put it up on my WordPress ViroBlogy site. This actually marked the start of a new endeavour to supply up-to-date information to students of virology, as well as interested lay folk, despite the fact that I was not teaching undergrads between 2010 and 2017 because of secondment to a job as Academic Liaison to UCT’s Research Portal Project.
What this has led up to, as I am now teaching undergraduates again, is the use of my Web-based news and other people’s materials via Twitter to inform students in the various modules I teach about current outbreaks, new discoveries and exciting developments in Virology and One Health. I tell them upfront in my first lecture that I want them to look at @edrybicki, ViroBlogy and Virology News, and that I will regularly be highlighting things of relevance to them. For instance, my daily trawl through Twitter invariably throws up a few papers I want to read, papers I think students should be interested in, and some news on outbreaks or breakthroughs. I then simply hashtag those with the course code, possibly add a comment, and retweet.
The value of this exercise can be seen in the fact that even well after I finished lecturing, students in the MCB2020F course were able to pick up on outbreak information that simply didn’t exist in that 5-lecture window weeks earlier – and give me material back in their final exam answers to the question “Describe one important virus disease outbreak this year and what it affected [3 marks]” that I had not taught them, from as short a time as 5 days previously. Which I commemorated thus, while marking their exam B-)
I did the same thing for a third-year Viromics course, and while I got fewer non-lecture material-based answers, the value of pointing students to alternative material was again confirmed.
I shall continue to do this over the next three years of formal lecturing, for the simple reason that it engages students in the productive use of social media – and makes them go out and find information you didn’t have to teach them.