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01 February 2021 | Story Prof Felicity Burt, Prof Dominique Goedhals & Dr Sabeehah Vawda | Photo istock

Opinion article by Prof Felicity Burt, Prof Dominique Goedhals, and Dr Sabeehah Vawda, Division of Virology, Faculty of Health Sciences, University of the Free State and National Health Laboratory Service, Bloemfontein. 

As we optimistically embarked on a new year with hopes of seeing an end to the global pandemic, masks, and social restrictions, our news channels were consumed with stories about virus variants and vaccine roll-out. What do these variants mean and will the vaccines protect against the changes that have emerged in the virus and save us from the new normal?

The news of a ‘mutated’ virus most likely conjures movie-like images of an invisible, indestructible enemy causing massive disruption. The reality is fortunately much less dramatic, as these changes are actually expected. Just to reiterate, severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has an RNA genome that codes for all the proteins which the virus produces. The exact details of how the virus replicates and produces new progeny, although of interest, are beyond the scope of this article. It is sufficient at this point to merely acknowledge that, during replication, the mechanism employed by viruses with an RNA genome allows for the introduction of mutations in the genes that code for the viral proteins. This is expected to occur and there is substantial evidence that the SARS-CoV-2 viral genes have evolved and adapted globally. Some mutations are silent, in other words, they do not change the viral proteins. However, in some instances the changes can affect the proteins encoded by the virus. If these changes occur in regions of the protein responsible for binding to the cell receptors that facilitate entry of the virus into the cell, or in regions of the protein that induce an immune response, the virus may show new characteristics, such as more successful transmission or escape from an existing immune response. 

Second wave of infections

South Africa and the United Kingdom are probably the two countries globally that have methodically sequenced the largest number of SARS-CoV-2 viruses isolated from patients. This technique allows the determination of the complete genome of each isolate and subsequent comparison, using bioinformatic software specifically designed to compare and identify changes and mutations in the nucleotide sequences. As we are all now aware, scientists in these two countries have identified virus variants with an accumulation of mutations and deletions occurring in the gene that encodes for the viral spike protein associated with binding to cell receptors and inducing protective immune responses. These variants have now become the predominant lineages circulating within local communities. 

In December 2020, scientists in South Africa revealed the presence of a variant of concern (VOC), now referred to as 501Y.V2. Sequence data confirmed that this variant initially emerged in October 2020, and by January 2021 it was present in multiple provinces in the country and is considered to be responsible for a significant number of cases occurring in the second wave of infections in the country. A second VOC reported by scientists in the United Kingdom in December 2020, (202012/01) likely emerged during September 2020. A third VOC has been reported from Brazil and is simply known as variant P1. To date, variant 501Y.V2 has been reported from at least 23 countries. VOC 202012/01 has been reported in at least 60 countries, and although the cases were initially associated with travellers, there is an increasing number of clusters of cases occurring in people with no history of travel. The United States, Israel, and India currently have the highest number of cases associated with this variant outside of the UK, keeping in mind that at the rate at which the pandemic unfolds, these statistics quickly become outdated. In contrast, variant P1 has only been reported from Brazil, and outside of Brazil it has been associated with travellers in a small number of countries. 

Immune responses

Changes in viral proteins may or may not influence certain characteristics of a viral infection. Current epidemiological data and modelling have all suggested that the VOC circulating in South Africa and the UK are more transmissible than previous lineages of the SARS-CoV-2. Despite the increased transmissibility, to date the severity of illness and the proportion of severe disease in different age groups appear to be unaffected by the changes in the protein. The increased transmissibility has increased the burden on the public and private health systems, emphasising the importance of rolling out a vaccine to healthcare workers and persons at increased risk of severe illness. 

The changes in the spike protein responsible for inducing immune responses have sparked research studies to determine whether the vaccines will be able to protect against the new variants.  It must be remembered that there are two arms to the immune response with complex interactions, and that natural protection will likely be a combination of responses. However, the presence of antibodies that neutralise the virus, in other words, block it from entering cells, and the ability of these neutralising antibodies to block new variants from entering the cells, can be investigated in the laboratory. Although the exact responses required for protection are not fully understood and will require studies that take more time to complete, an indication of neutralising capacity provides some information with regard to the potential efficacy of the vaccine against variants. What we currently know from laboratory research is that there is a reduction in the ability of antibody from people previously infected during the first wave of cases to neutralise the new variant circulating in South Africa. This reduction varied among the cohort of samples tested, but overall, there was a weaker neutralising capability. Similar results were demonstrated using pseudoviruses representing the variant virus. Studies looking at antibodies in people who have been vaccinated show similar reductions in neutralisation. The answer is unfortunately not clear at this stage, with many pieces of the puzzle still to be determined. The reduced capacity to neutralise in a laboratory was not what we wanted to hear, but it must be remembered that vaccines induce a broad immune response and not only neutralise antibody, and hence there are other components to the immune response that will likely contribute to protection. Nonetheless, even a reduced immune response will contribute towards vaccine-induced herd immunity and saving lives by preventing severe disease. 

Vaccine trials

In addition to the vaccines currently in use, results were released from clinical trials using vaccines from Novavax and Johnson & Johnson. Although a lower efficacy was shown among the South African population compared to results obtained in the UK, the efficacy was still in the region of 57% to 60%, which is certainly encouraging in view of the new variant circulating. The differences observed illustrate the importance of conducting vaccine trials in local populations. An efficacy of 60% will still contribute towards herd immunity and the prevention of severe disease, emphasising the importance of a rapid roll-out and hopefully a high uptake of the vaccine. Vaccination will not only protect the vaccinee but should contribute to minimising the risk of further variants emerging. 

The roll-out of vaccine, further research on immune responses in vaccinated communities, epidemiological data, and sequence data will all contribute towards monitoring the evolution of the outbreak. Flu vaccines are modified annually and if the COVID-19 vaccine needs to be modified, manufacturers have the capability to do this, and some have already started this process. 

Additional waves of infection are predicted to occur until herd immunity can be achieved. Whether the current variants will be responsible for the next wave is not possible to predict, and continued research analysing the gene sequences of future isolates will play an important role in determining how the virus is evolving. 

In the interim, until we have sufficient vaccine-induced herd immunity to provide protection, non-pharmaceutical interventions and human behaviour will continue to play the important role of minimising new infections. To quote CS Lewis: “You can’t go back and change the beginning, but you can start where you are and change the ending.”

 

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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