“This is a landmark moment for South Africa and Africa at this stage of the Covid-19 pandemic,” Professor Shabir Madhi said at the launch of the South African Ox1Cov-19 Vaccine VIDA-Trial. “As we enter winter in SA and pressure increases on public hospitals, now more than ever we need a vaccine to prevent infection by Covid-19.” Professor of Vaccinology at Wits University and director of the South Africa Medical Research Council (SAMRC) Vaccines and Infectious Diseases Analytics Research Unit (VIDA), Prof Shabir Madhi leads the South African Ox1Cov-19 Vaccine VIDA-Trial which aims to find a vaccine that will prevent infection by SARS-CoV-2, the virus that causes Covid-19.

The first vaccine trial participants in SA were vaccinated on 25 June, with complete enrollment across multiple sites expected by mid-August [Image: kjpargeter/Freepik].

THE VACCINE

Developed at the Oxford Jenner Institute, the ChAdOx1 nCov-19 the vaccine was made by adding genetic material – called spike glycoprotein – that is expressed on the surface of SARS-CoV-2 to the ChAdOx1 virus. Usually found on the surface of the novel coronavirus, this spike glycoprotein is what gives the coronavirus its distinct spiky appearance. These spikes play an essential role in laying a path for infection by the coronavirus.

The virus that causes Covid-19 uses this spike protein to bind to ACE2 receptors on human cells. ACE2 is a protein on the surface of many cell types. It is an enzyme that generates small proteins that then go on to regulate functions in the cell. In this way, the virus gains entry to the cells in the human body and causes Covid-19 infection. Researchers have shown that antibodies produced against sections of the spike protein after natural infection are able to kill the virus when tested in the laboratory.

By vaccinating volunteers with ChAdOx1 nCoV-19, scientists hope to make the human body recognise and develop antibodies to the spike glycoprotein that will help stop the SARS-CoV-2 virus from entering human cells and causing Covid-19.

THE TRIAL

The first participants in SA were vaccinated on 25 June, with complete enrolment across multiple sites expected by mid-August. The study is being undertaken in urban metropoles where the risk of SARS-CoV2 infection is high, and which are likely to be Covid-19 hotspots. Although current sites are in Gauteng, the study may be extended to sites in Cape Town too. “The study aims to enrol 1 950 adult volunteers aged 18-65 years and who are HIV negative. They should not have tested positive for Covid-19 and should not be pregnant or breast-feeding, nor have previously participated in a trial with an adenoviral vaccine or received any other coronavirus vaccine,” said Prof Madhi.

“The trial will also enrol a smaller number (50) of people living with HIV to examine the safety and how well they respond to the vaccine. While half of the participants will receive the ChAdOx1 nCoV-19 vaccine, the other half will receive a placebo (normal saline). There will be planned follow-ups, up to 12 months after vaccination and participants will have fortnightly appointments to assess for any respiratory illness. They will also be investigated for Covid-19 in the event they fulfill criteria that indicate illness,” he said.

ONE OF 3

The trial is one of three currently being run. The ChAdOx1 nCov-19 vaccine is already being evaluated in a large clinical trial in the UK where more than 4 000 participants have been enrolled. In addition to the SA study, similar and related studies are about to start in Brazil. An even larger study of the same vaccine of up to 30 000 participants is planned in the USA.

“It is essential that vaccine studies are performed in southern hemisphere countries, including in the African region, concurrently with studies in northern hemisphere countries,” said Professor Helen Rees, chair of the South African Health Products Regulatory Authority (SAHPRA) and executive director of the Wits Reproductive Health and HIV Institute (Wits RHI).

“This allows evaluation of the efficacy and safety of candidate vaccines to be assessed in a global context, failing which the introduction of many life-saving vaccines into public immunisation programmes for low-middle income countries frequently lags behind those in high-income countries.”

REALISTIC EXPECTATIONS

Although the development of this vaccine is on accelerated timeline to address the unprecedented pandemic that we face, Prof Madhi explained it usually takes 5-10 years to develop a vaccine. “We are trying to condense that into 1-2 years. Furthermore, one must remember the chances of success of any human trial is only around 10% because of stringent assessment of safety and efficacy.

“We are hoping to get an answer by the end of this year but that doesn’t mean the vaccine will be available then. It would still need to be reviewed, and then we would need manufacturing facilities that can produce the vaccine. So, the best-case scenario in terms of when it might become available would probably be in the third quarter of 2021.”

THE RACE TO A VACCINE

Although there are more than 100 Covid-19 vaccines currently in development, a significant proportion of vaccines that are tested in clinical trial are found not to be suitable for further development. The ChAdOx1-Cov19 vaccine is one of only five vaccines that are currently in the clinical development phase in humans, with the studies mainly being done in China, USA, UK, Australia and Europe.

Monitored intensely by an independent Data, Safety and Management Committee, which includes a leading SA scientist, Prof Madhi explained if the SA trial is unable to show that the vaccine protects against Covid-19, or that it is not safe, progress will be reviewed and alternative approaches explored.

“As the world rallies to find health solutions, a South African endeavour for the development of an effective Covid-19 vaccine is testament to our commitment of supporting healthcare innovation to save lives,” Professor Glenda Gray, president and CEO of the SAMRC, said at the launch.

Funded locally by the SAMRC through a grant from the Bill & Melinda Gates Foundation, Prof Madhi said the total cost of the SA study is about R150 million.

WHERE WE STAND RIGHT NOW

The day after the launch Prof Madhi raised concerns around the true number of positive Covid-19 cases in SA during a MyHealthTV webinar. “When we say we have reached 100 000 cases, that is a complete underestimate. In my estimate, it is close to ten times more – probably around a million people. There is increasing evidence that many are asymptomatic but are still spreaders.

“We are still in the first wave and we are probably going to experience three to four waves over the next two years. We haven’t even peaked, not even in the Western Cape. It will be completely dependent on the behaviour of South Africans rather than government interventions as to what the peak looks like. Citizens adhering to the non-pharmaceutical interventions is the single most important factor to prevent more peaks. It slows the rate of transmission,” he said.

As such, social distancing, hand washing, and the wearing of masks remain the most important things South African’s can do to curb the spread of Covid-19.