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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

Inaugural lecture: Prof Robert Bragg, Dept. of Microbial, Biochemical and Food Biotechnology
2006-05-17



Attending the inaugural lecture were in front from the left Prof Robert Bragg (lecturer at the Department of Microbial, Biochemical and Food Biotechnology) and Frederick Fourie (Rector and Vice-Chancellor).  At the back from the left were Prof James du Preez (Departmental Chairperson:  Department of Microbial, Biochemical and Food Biotechnology) and Prof Herman van Schalkwyk (Dean: Faculty of Natural and Agricultural Sciences). Photo: Stephen Collett
 

A summary of an inaugural lecture delivered by Prof Robert Bragg at the University of the Free State:

CONTROL OF INFECTIOUS AVIAN DISEASES – LESSONS FOR MAN?

Prof Robert R Bragg
Department of Microbial, Biochemical and Food Biotechnology
University of the Free State

“Many of the lessons learnt in disease control in poultry will have application on human medicine,” said Prof Robert Bragg, lecturer at the University of the Free State’s (UFS) Department of Microbial, Biochemical and Food Biotechnology during his inaugural lecture.

Prof Bragg said the development of vaccines remains the main stay of disease control in humans as well as in avian species.  Disease control can not rely on vaccination alone and other disease-control options must be examined.  

“With the increasing problems of antibiotic resistance, the use of disinfection and bio security are becoming more important,” he said.

“Avian influenza (AI) is an example of a disease which can spread from birds to humans.  Hopefully this virus will not develop human to human transmission,” said Prof Bragg.

According to Prof Bragg, South Africa is not on the migration route of water birds, which are the main transmitters of AI.  “This makes South Africa one of the countries less likely to get the disease,” he said.

If the AI virus does develop human to human transmission, it could make the 1918 flu pandemic pale into insignificance.  During the 1918 flu pandemic, the virus had a mortality rate of only 3%, yet more than 50 million people died.

Although the AI virus has not developed human-to-human transmission, all human cases have been related to direct contact with infected birds. The mortality rate in humans who have contracted this virus is 67%.

“Apart from the obvious fears for the human population, this virus is a very serious poultry pathogen and can cause 100% mortality in poultry populations.  Poultry meat and egg production is the staple protein source in most countries around the world. The virus is currently devastating the poultry industry world-wide,” said Prof Bragg.

Prof Bragg’s research activities on avian diseases started off with the investigation of diseases in poultry.  “The average life cycle of a broiler chicken is 42 days.  After this short time, they are slaughtered.  As a result of the short generation time in poultry, one can observe changes in microbial populations as a result of the use of vaccines, antibiotics and disinfectants,” said Prof Bragg.   

“Much of my research effort has been directed towards the control of infectious coryza in layers, which is caused by the bacterium Avibacterium paragallinarum.  This disease is a type of sinusitis in the layer chickens and can cause a drop in egg product of up to 40%,” said Prof Bragg.

The vaccines used around the world in an attempt to control this disease are all inactivated vaccines. One of the most important points is the selection of the correct strains of the bacterium to use in the vaccine.

Prof Bragg established that in South Africa, there are four different serovars of the bacterium and one of these, the serovar C-3 strain, was believed to be unique to Southern Africa. He also recently discovered this serovar for the first time in Israel, thus indicating that this serovar might have a wider distribution than originally believed.

Vaccines used in this country did not contain this serovar.  Prof Bragg established that the long term use of vaccines not containing the local South African strain resulted in a shift in the population distribution of the pathogen.

Prof Bragg’s research activities also include disease control in parrots and pigeons.   “One of the main research projects in my group is on the disease in parrots caused by the circovirus Beak and Feather Disease virus. This virus causes serious problems in the parrot breeding industry in this country. This virus is also threatening the highly endangered and endemic Cape Parrot,” said Prof Bragg.

Prof Bragg’s research group is currently working on the development of a DNA vaccine which will assist in the control of the disease, not only in the parrot breeding industry, but also to help the highly endangered Cape Parrot in its battle for survival.

“Not all of our research efforts are directed towards infectious coryza or the Beak and Feather Disease virus.  One of my Masters students is currently investigating the cell receptors involved in the binding of Newcastle Disease virus to cancerous cells and normal cells of humans. This work will also eventually lead to a possible treatment of cancer in humans and will assist with the development of a recombinant vaccine for Newcastle disease virus,” said Prof Bragg.

We are also currently investigating an “unknown” virus which causes disease problems in poultry in the Western Cape,” said Prof Bragg.
 
“Although disinfection has been extensively used in the poultry industry, it has only been done at the pre-placement stage. In other words, disinfectants are used before the birds are placed into the house. Once the birds are placed, all use of disinfectants stops,” said Prof Bragg.

“Disinfection and bio security can be seen as the ‘Cinderella’ of disease control in poultry.  This is also true for human medicine. One just has to look at the high numbers of people who die from hospital-acquired infections to realise that disinfection is not a concept which is really clear in human health care,” said Prof Bragg.

Much research has been done in the control of diseases through vaccination and through the use of antibiotics. “These pillars of disease control are, however, starting to crumble and more effort is needed on disinfection and bio security,” said Prof Bragg.

Prof Bragg has been working in close co-operation with a chemical manufacturing company in Stellenbosch to develop a unique disinfectant which his highly effective yet not toxic to the birds.

As a result of this unique product, he has developed the continual disinfection program for use in poultry. In this program the disinfectant is used throughout the production cycle of the birds. It is also used to ensure that there is excellent pre-placement disinfection.

“The program is extensively used for the control of infectious diseases in the parrot-breeding industry in South Africa and the product has been registered in 15 countries around the world with registration in the USA in the final process,” said Prof Bragg.

“Although the problem of plasmid mediated resistance to disinfectants is starting to rear its ugly head, this has allowed for the opening of a new research field which my group will hopefully exploit in the near future,” he said.

 

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