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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 receives R13,7 Million for Research into Prehistoric Organisms
2007-03-27

Some of the guests attending the launch of the research contract are: Dr Siyabulela Ntutela (Deputy Director: Biotechnology at the Department of Science and Technology), Dr Godfrey Netswera (Manager of Thuthuka and the Support Programme at the National Research Foundation (NRF)), Dr Esta van Heerden (Platform Manager and lecturer at the Department of Microbial, Biochemical and Food Biotechnology at the UFS), Mr Butana Mboniswa (Chief Executive Officer of BioPAD), and Mr Vuyisele Phehani (Portfolio Manager for BioPAD).
Photo: Leonie Bolleurs

The University of the Free State (UFS) has been awarded a massive R13,7 million contract to conduct research into prehistoric micro-organisms which live under extreme conditions, for example in mineshafts.

This is one of the biggest research contracts awarded to the UFS in recent years.

The biotechnology research contract was awarded to the UFS by BioPAD, a South African biotechnology company that brokers partnerships between researchers, entrepreneurs, business, government and other stakeholders to promote innovation and create sustainable biotechnology businesses.

The project is endorsed by the Department of Science and Technology and the National Research Foundation (NRF), which contributes to the bursaries of the 17 postgraduate students on the programme.

The contract involves the establishment of a Platform for Metagenomics -  a technique which allows researchers to extract the DNA from microbes in their natural environment and investigate it in a laboratory. 

“Through this platform we will be able to understand deepmine microbial populations
and their potential application in the search for life in outer space.  It is most likely
that, if life were to be found on other planets in our solar system, it would probably
resemble that which existed millions of years ago on earth.  Apart from all this, these
organisms have unique properties one can exploit in biotechnological application for
South Africa and its community,” said Dr Esta van Heerden, platform manager and
lecturer at the UFS Department of Microbial, Biochemical and Food Biotechnology.
She is assisted by her collegues, Prof. Derek Litthauer and Dr Lizelle Piater.

“The platform aims to tap into the unique genetic material in South African mines
which will lead to the discovery of new genes and their products.  These new and unique products will find application in the medical field (anti-cancer, anti-bacterial en anti-viral cures), the industrial sector (nanotechnology, commercial washing agents and the food industry), environmental sector (pollution management, demolition of harmful metals and other toxic waste),” said Dr Van Heerden.

According to Dr Van Heerden, the Metagenomics Platforms stems from the Life in
Extreme Environments (LExEN) programme which was started in 1994 by Princeton
University in the United States of America (USA) in South African mines with grants
from among others the National Aeronautics and Space Administration (NASA) and
the National Science Foundation (NSF) in the USA.  Other international collaborators
on the project include Geosynec Consultants Inc. (USA), Oak Ridge National
Laboratory (USA), the University of Tennessee (USA) and in South Africa the
Universities of the Witwatersrand, North West and Limpopo and companies like BHP
Billiton, MINTEK and mining companies like Harmony, Gold Fields and AngloGold
Ashanti.

The research field laboratory of the Metagenomics Platform, which was situated in
Glen Harvey, was moved to the Main Campus of the UFS in Bloemfontein.  “In this
way the university has become the central hub for all research programmes.  We are
also the liaison between the LExEN programme and the various mining companies
involved,” said Dr Van Heerden.  The new laboratory was introduced during the
launch of the research contract.

“Our decision to commit BioPAD to this project stems from the company’s commitment to advance human capacity development to strengthen South Africa’s research infrastructure.  It is also part of our aim to create and protect intellectual property,” said Mr Butana Mboniswa, Chief Executive Officer of BioPAD.

Talking on behalf of the UFS senior management, Prof. Teuns Verschoor, Vice-Rector
of Academic Operations, said that the university shares the excitement to be part of
the exploration of unknown forms of life, the discovery of new genes and
their products and in applying newly gained knowledge to better understand our
universe.

Media release
Issued by: Lacea Loader
Assistant Director: Media Liaison 
Tel: 051 401 2584
Cell: 083 645 2454
E-mail: loaderl@ufs.ac.za
27 March 2007

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