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UFS research team contributes to COVID-19 vaccine development

31 March 2020 | Story Leonie Bolleurs | Photo Supplied

UFS Covid-19 vaccine research team — Prof Robert Bragg and members of the Veterinary Biotechnology research group believe that finding a vaccine for COVID-19 will not be a ‘quick fix’. From the left are: Prof Bragg, Samantha McCarlie, Liese Kilian, and Dr Charlotte Boucher-van Jaarsveld. The photo was taken during the World Veterinary Poultry Association congress in Thailand in 2019.

On 31 March 2020, there were 804 061 coronavirus cases and 39 064 deaths globally due to the outbreak. According to media reports, there is still no licensed vaccine for COVID-2019 – the cause of our current global health emergency.

Prof Robert Bragg, researcher at the University of the Free State (UFS), says this is without a doubt the most pressing research need in the world today.

The Veterinary Biotechnology research group in the Department of Microbial, Biochemical, and Food Biotechnology at the UFS recently submitted an article for publication on the design of a possible COVID-19 vaccine, based on work they have done on infectious bronchitis virus (also a coronavirus). The article, authored by the group of which Prof Bragg is a member, is titled: A sub-unit vaccine produced in 'Yarrowia lipolytica' against COVID-19: Lessons learnt from infectious bronchitis virus.

The research group, consisting of researchers and postgraduate students, is mostly looking at strategies for improved disease control, mainly in avian species, through vaccine development, treatment, and biosecurity.

Prof Bragg says their main aim with this study was to get the research out there so that the bigger pharmaceutical companies could take up the design of a possible COVID-19 vaccine and assist with the development of a vaccine.

He says the research group’s role in this lengthy process would be to express the protein, which could be used in the development of a possible vaccine. “Thereafter, it will have to be taken up by a vaccine manufacturer to get the vaccine made and to the market.”

Developing a vaccine
Liese Kilian, a member of the research group, finished writing up her MSc thesis in Microbiology in the UFS Department of Microbial, Biochemical, and Food Biotechnology in December 2019 – the same time that COVID-19 originated in China. She has been working on the development of an edible sub-unit vaccine against the infectious bronchitis virus (IBV), which is a widespread avian coronavirus. This virus is specific to poultry and is different from COVID-19.

Kilian’s project was conducted under the supervision of Prof Bragg and Dr Charlotte Boucher-van Jaarsveld. Dr Boucher-van Jaarsveld is a research fellow in the university’s Department of Microbial, Biochemical and Food Biotechnology.

Kilian, with the assistance of Samantha Mc Carlie, currently a master’s student in the research group, substituted the genetic code of the IBV with the genetic code of the COVID-19 virus, which were already published at that stage. Thus, a gene for the development of a possible sub-unit vaccine against the S1 spike protein of COVID-19 was developed for expression in the same yeast strain used to express the spike protein of IBV. A sub-unit vaccine can be described as part of a pathogen, triggering an immune response against the pathogen from which it is derived.

After Killian successfully developed the gene for this study, she expressed the S1 spike protein of the IBV in a yeast-based expression system developed by the research group. Dr Boucher-van Jaarsveld says this simply means that the yeast takes up the foreign genetic material (viral gene) into its own genetic make-up and makes more of this protein as if it is part of the yeast’s normal material.

“The images of COVID-19 are being shown constantly in the media and the ‘spikes’ can be seen on all of these images. These spikes are very typical for all coronaviruses and there is some level of similarity between the structure of these spikes in many of the coronaviruses,” Prof Bragg adds.

According to the World Health Organisation, the spike protein is a promising candidate for a sub-unit vaccine due to its immunogenicity and safety, as well as manufacturing and stability considerations during large-scale development.

Prof Bragg says there are many different expression systems that are widely used. Producing the sub-unit vaccine in a yeast species is beneficial for the work they are doing. A yeast expression system is favourable as large-scale production, is less expensive compared to mammalian cell lines, and can be applied as an edible vaccine.

“The technology to grow massive volumes of yeast are also very well established. This, after all, is how beer is made!” Prof Bragg says. Dr Boucher-van Jaarsveld adds: “The expression of an antigen is not necessarily just geared towards vaccines but can also be used in the development of diagnostic tests to screen populations for infections.”

Working with other researchers
“Now that the situation is all but out of control, we maybe need to investigate the possibilities of working with other key researchers at the UFS as well as other universities in South Africa to develop the vaccine or diagnostic reagents locally. Discussions on this aspect are already underway.”

Several other universities in South Africa are also working to find a cure for the virus. Government availed funding for more research on the matter. According to Higher Education, Science and Technology Minister, Blade Nzimande, the University of Cape Town, the Council for Scientific and Industrial Research, as well as the Vaccines Institute of Southern Africa are working on the development of a vaccine.

Prof Bragg expressed the hope of obtaining funding for this work. “Because without funding, we will not be able to do anything with this data,” he says. They are currently investigating different funding options.

“The sooner we start on the development of a vaccine, the sooner there will be one, but it will not be a ‘quick fix’. It must be stressed that, even if vaccine development is fast-tracked through the regulatory bodies, it will take many months (if not years) to move from the laboratory to the first human experimentation. It will take even longer before any human vaccine can be rolled out,” says Prof Bragg.

News Archive

Research by experts published in Nature

2011-06-02

The members of the research group are, from the left, front: Christelle van Rooyen, Mariana Erasmus, Prof. Esta van Heerden; back: Armand Bester and Prof. Derek Litthauer.
Photo: Gerhard Louw

A research article on the work by a team of experts at our university, under the leadership of Prof. Esta van Heerden, and counterparts in Belgium and the USA has been published in the distinguished academic journal Nature today (Thursday, 2 June 2011).

The article – Nematoda from the terrestrial deep subsurface of South Africa – sheds more light on life in the form of a small worm living under extreme conditions in deep hot mines. It was discovered 1,3 km under the surface of the earth in the Beatrix Goldmine close to Welkom and is the first multi-cellular organism that was found so far beneath the surface of the earth. The worm (nematode) was found in between a rock face that is between 3 000 and 12 000 years old.

The research can shed some new light on the possibility of life on other planets, previously considered impossible under extreme conditions. It also expands the possibilities into new areas where new organisms may be found.

These small invertebrates live in terrestrial soil subjected to stress almost for 24 hours They live through sunshine, rain, scorching temperatures and freezing conditions. Through time they developed a means to cope with harsh conditions. Terrestrial nematodes (roundworms, not to be confused or related to earthworms) are among those very tough small invertebrates that deal with those conditions everywhere. After insects they are the most dominant multi-cellular (metazoan) species on the planet having a general size of 0,5 to 1 mm and are among the oldest metazoans on the planet, Nature says in a statement on the article.

They inhabit nearly every imaginable habitat form the deep seas to the acid in pitcher . Some nematodes simply eat bacteria and these are the ones we study here. Terrestrial nematodes have developed a survival stage that can take them through hard times (absence of food, extreme temperatures, too little oxygen, crowding, and more).

At the head of the research was Prof. Gaetan Borgonie of the Ghent University in Belgium and a world leader in the discipline of nematode research. He was brought into contact with the South African research leader, Prof. Esta van Heerden, who set up a cooperation agreement with the University of Ghent and Prof. Borgonie. Prof. Van Heerden manages the Extreme Biochemistry group at the UFS and the research was funded by several research grants.

The search for worms began in earnest in 2007, but it was soon clear that the sampling strategy was insufficient. A massive sampling campaign in 2008-2009 in several mines led to the discovery of several nematodes and the new nematode species Halicephalobus mephisto. It is named after the legend of Faust where the devil, also known as the lord of the underworld is called Mephistopheles.

Nature says special filters had to be designed and installed on various boreholes. Unfortunately, there is no easy way of finding a magic formula and designs had to be adapted by trial and error; improving existing designs all the time. The work of the UFS Mechanical Workshop, which manufactured, adapted and helped design it, was crucial in this respect. Filters were left on the holes for varying periods, sometimes for a few hours and sometimes for months. Prof. Derek Litthauer from the UFS played a big role in sampling, filter designs and coming up with ideas for names for the new nematode with Prof. Borgonie.

Research showed that the nematodes can live in the deep for up to 12 000 years. Three students – Armand Bester, Mariana Erasmus and Christelle van Rooyen from the UFS – did the work on this.

The importance of multi-cellular animals living in the ultra-deep subsurface is twofold: The nematodes graze on the existing bacterial population and influence their turnover. Secondly, if more complex multi-cellular organisms can survive in the deep subsurface on earth, this may be good news when looking for life on other planets where the surface is considered too inhospitable (e.g. Mars). Complex life forms can be found in ecosystems previously thought to be uninhabitable. Nature says this expands the possibilities into new areas where new organisms may be discovered.

Future research will focus on selective boreholes to look for more metazoans, so that a better idea of the complexity of the ecosystems there can be obtained. It will also look for metazoans in the deep subsurface on other continents to determine similarities and differences.

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