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Variants, vaccines, and virology – are we protected?

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

Conference: Expanded ARV treatment

2005-03-02

VENUE: University of the Free State, Bloemfontein, South Africa
DATE: 30 March 2005 - 1 April 2005

ARV Programme as on 24Feb Download Word document
Programme Special events Download Word document

Official web site www.fshealth.gov.za/subsites/arvc

Rationale for the Conference
At the time of the planned Conference, much ground would have been covered, both in the Free State and in South Africa, in respect of the expanded public sector ARV treatment programme in respect of research, experiences in practice, training of staff, treatment of patients, lessons learned, successes and failures, etc. The time would then be quite opportune to share these in a systematic manner with other provinces and countries, as well as with the large variety of stakeholders and role players in the ARV and related domains, be they academics and researchers, policy makers and service/facility managers, the variety of caregivers, and the community organisations and affected patients.

The Conference and current research
The proposed Conference is, firstly, directly linked to the current research on the public sector roll-out of ARV treatment in the Free State conducted by several research institutions (e.g. CIET, CHSR&D, UCT Lung Institute). Secondly, the Conference could and would serve as a forum for other research groups in the country and further a field to report and share knowledge and experiences on ARV treatment and related initiatives. Lastly, the Conference will stage a golden opportunity for researchers and scientists, on the one hand, and policy makers, managers, and caregivers (as knowledge users), on the other hand, to engage in cross-disciplinary discourse on this mutual and topical theme.

Theme of Conference
Expanded ARV treatment in the Free State: sharing experiences

Focus
The focus is primarily on public sector ARV treatment in the Free State, but also initiatives/activities/perspectives of relevance to the Free State elsewhere in the country at large and further a field, as well as relevant ARV initiatives in the public, private, NGO and FBO sectors. Bear in mind, however, that ARV treatment is but part of a much more comprehensive approach to HIV and AIDS. The Conference will, therefore, not narrowly focus on the ARV treatment programme only. The broader context, other relevant dimensions, and a comprehensive approach to the challenges of HIV, AIDS and TB are of equal importance.

The purpose of the Conference
Enhance meaningful exchange, mutual understanding and collaboration among researchers, scientists, policy makers, managers and practitioners in the field of ARV treatment and related fields.

Share experiences in the various spheres of ARV treatment and related spheres (policy, management, practice, research, training, public-private-civil society sectors).

Record, reflect and report on the establishment of the ARV treatment programme in the Free State, and in within the context of the comprehensive HIV/AIDS programme.

Disseminate important research results on ARV treatment and related themes to health policy makers, managers, practitioners, communities and to the research community.

Stimulate discourse among various disciplines and various stakeholders/role players involved in ARV treatment and related programmes.

Sensitise and acquaint researchers to the requirements of policy makers, managers and practitioners in respect of ARV treatment and related fields.

Facilitate the implementation of research results in ARV treatment policy, programmes and practice.

Dissemination of Conference-related information
Information generated during the Conference could feed into policy, management and practice of ARV treatment, the training accompanying such programme, and the existing body of knowledge. After the Conference the information will be disseminated via the Internet and by scientific and popular publications.

Date and duration
Set for 30 & 31 March & 1 April 2005; to commence at 09:00 on the first day (30 March) and to end at 16:30 (1 April) the third day.

Format and scope of Conference
Alternating plenary, parallel sessions and debates focused on topical issues and interest groups. The Conference will strive to be maximally interactive and participative.

Themes and topics to cover:

Policy, management and health services/practice (various levels and contexts – clinical treatment, information, IT systems, pharmacy, laboratories, nutrition)
Research covering all relevant disciplines and diverse dimensions of ARV treatment and related themes
Training and evaluation of training
Patients, communities and civil society organisations
Public, private, NGO, FBO initiatives and partnerships

Emphasis will be on the Free State, however, with of significant involvement from other provinces, SADC countries, and countries further a field. The thrust will be to export lessons and experiences from the Free State, but also to import lessons and experiences from other provinces, countries and sectors.

Presenters
Key presenters from the Free State, other provinces, South Africa, from the private, FBO and NGO sectors, and from several other countries

Delegates
About half of the delegates will be Free State stakeholders and role players (all levels and all contexts). The other half will be role players and stakeholders in the ARV and related fields from other provinces, the national level, and other countries, as well as from the private, public and non-governmental sectors.

Focused workshops
Provision will be made for half-a-day or one-day workshop initiatives on the third day (1 April 2005).

Enquiries
For more information please contact:

Prof Dingie van Rensburg
Centre for Health Systems Research & Development
University of the Free State
PO Box 339
Bloenfontein
SOUTH AFRICA
9300

Contact:
Carin van Vuuren
Conference Organiser
Centre for Health Systems Research & Development
University of the Free State
P.O.Box 339
Bloemfontein
South Africa
9300
Tel +27 (0) 51 401 2181
Fax +27 (0) 51 4480370
Cell 0832932890
e-mail: arvconference.hum@mail.uovs.ac.za

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