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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

UFS hones focus to nurture world-class research - Business Day
2006-02-10

 

Sue Blaine
THE University of the Free State plans to concentrate academic study in five areas to strengthen its status as a research institution, the university said yesterday.

The Bloemfontein-based university will focus on areas it classes as development (economics, health, literacy and other human activities) and social transformation — an analysis of how South African society is changing from a philosophical and political viewpoint.

The other three research areas are new technologies, water resources and security, and food production and security.

“It makes sense to concentrate the university’s human resources, infrastructure, financial resources and intellectual expertise,” said university rector and vice-chancellor Prof Frederick Fourie.

The move introduces a style of research that matches international trends.

Universities in Canada, Britain and Australia are setting up their research departments in this way.

In SA, the universities of Stellenbosch, the Witwatersrand, Cape Town and KwaZulu-Natal have embarked on similar strategies.

Fourie gave the example of his alma mater, the US’s Harvard University, whose Nanoscale Science and Engineering Centre is an example of “clustering” on a larger scale.

The centre is a collaboration with Harvard, the Massachusetts Institute of Technology, the University of California, Santa Barbara, the Museum of Science, Boston, and universities in the Netherlands, Switzerland and Japan.

Fourie said the modern research world was so diverse and complex that no university could cover all bases so it was better to establish areas of expertise that made it different from its peer institutions.

Having scientists and researchers work in teams meant certain issues could be researched and developed in a multidisciplinary manner. “I think it’s the only way in which any university can excel. This will help SA become world class in selected areas,” Fourie said.

It is in chemistry that the cluster model has already had its most visible results, with a slice of the university’s on-campus pharmacological testing company Farmovs, established in the 1980s, sold to the US’s Parexel International.

The company is one of the largest biopharmaceutical outsourcing organisations in the world, providing knowledge-based contract research, medical marketing and consulting services to the global pharmaceutical, biotechnology and medical device industries, according to Biospace, an internet-based company providing resources and information to the life science industry.

President Thabo Mbeki, in his state of the nation address last Friday, committed government to allocating more resources to research, development and innovation, and increasing the pool of young researchers in SA.

He said government would “continue to engage the leadership of our tertiary institutions focused on working with them to meet the nation’s expectations with regard to teaching and research”.

The university used to be home to several A-rated scientists, who are considered by a peer review, conducted by the National Research Foundation, to be world leaders in their fields, but had lost them to other institutions. Fourie hopes to lure them back, and with them postgraduate students and funding for their work.

“At universities where you get a star researcher they tend to attract people and funding; if they leave they take that with them,” he said.

Fourie said R50m would be spent on the project, with some already spent last year and the last disbursements to be made next year.

There is R10m in seed money to gather experts and improve equipment and infrastructure, and R17m has been invested in chemistry equipment and staff.

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