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.