Vaccine developments: Update on the SA trial, and more reaction to positive news from Oxford

  • SA's Covid-19 vaccine trial results are expected in November this year
  • Complete enrollment of all 2 000 participants will happen by mid-August
  • Trials for two more vaccine candidates may soon be underway

Earlier this month, Health24 reported that scientists leading the South African Covid-19 vaccine trial, named Ox1Cov-19 Vaccine VIDA-Trial, are expecting results as early as the end of November this year. Shabir Madhi, who is leading the SA trial and is also Professor of Vaccinology at the University of the Witwatersrand (Wits) in Johannesburg, expanded on this during an ECN (Economist Corporate Network) Africa webinar earlier this week.

“The plan is to enrol 2 000 participants, and we have currently enrolled just over 400 participants. We expect to complete the enrollment of the 2 000 participants by mid-August,” said Madhi.

Madhi further commented that based on the most recent data by the Oxford trial, which were released on Monday, South African participants would likely need to be given two doses of vaccine. (The results, published in The Lancet, showed that 90% of people developed neutralising antibodies after one dose, and of the ten people that were given two doses, all of them produced neutralising antibodies.)

Why SA’s sample size is comparatively low

Compared to the UK and Brazil who are also running trials on the same vaccine candidate (non-replicating viral vector) – as well as the US which is testing an RNA-based vaccine on their population – the number of participants involved in South Africa’s study is relatively small.

The UK has enrolled 4 000 participants and plans to enrol a further 10 000; Brazil’s study is underway and has enrolled approximately 5 000 participants; and the US plans to enrol 30 000 participants for their Moderna Phase 3 trial. This is all due to the timing of the vaccine study, explained Madhi.

“The timing of the vaccine study in South Africa is very different to the timing of the study in the UK, for example. In the UK, they’re moving towards the tail-end of the current wave of the outbreak, so they have very few infections taking place.

“On the other hand, in South Africa, we’re pretty much doing the study in the midst of the storm, so the infection rate is going to be higher,” said Madhi.

Two additional vaccine trials

According to Madhi, another two vaccine candidates are currently under review by the regulatory bodies, including SAMAREC (South African Medical Association Research Ethics Committee) and SAHPRA (South African Health Products Regulatory Authority). Should these be approved for trial, these vaccine studies will hopefully launch within the next two to three months.

Data credibility is a huge problem

Among the topics Madhi addressed was the huge underreporting of cases, especially in Africa. Madhi expressed that we must not be blinded by the systematic underestimates of how widespread Covid-19 truly is, including in South Africa.

“We just need to be a bit guarded and not spread the narrative of Africa being spared from Covid-19, because it has got implications of Africa being prioritised when it comes to access to vaccines,” said Madhi.

News24 reported on this exact concern this week, noting that, according to health experts, the official number of deaths linked to Covid-19 in the country doesn't reflect the true scale of the crisis. The article also explains that provinces that have been hit hardest by the outbreak have shown a surge in fatalities.

Reinfection and immunity against Covid-19

On whether immunity against Covid-19 is short-lived, as recent studies indicated, and whether it may become an annual event such as the seasonal flu, Madhi said the following:

“The reality is that around 90–95% of people infected with the virus have a mild or asymptomatic infection, and in those individuals, it seems that there’s much more rapid waning (decreasing) of antibodies – roughly by about one month – so that is of concern.

“If you develop more severe disease, the antibody persistence seems to be longer," adding that this, however, is only one part of our immune defence.

The role of antibodies and T-cells

Researchers of the Oxford vaccine trial found that the T-cell response did not increase with a second dose of the vaccine, but that the antibody response was boosted by a second dose of the vaccine.

Antibodies are proteins that are produced by cells (called B-cells), Professor Thomas Scriba, Deputy Director of Immunology and Laboratory Director at the University of Cape Town, explained to Health24.

“After natural infection or vaccination, these B-cells go sit on the bone marrow and produce antibodies. And with an excellent vaccine, those antibodies will persist at very high levels – in some cases for life (for example, the measles vaccination induces antibody levels that protect humans for life).

T-cells, on the other hand, do not produce antibodies – they are natural killers. Essentially, they find infected cells in the human body and destroy them. More importantly, Scriba explained, T-cells are important to help B-cells develop during the initiation of the immune response.

Oxford finding not surprising

The fact that antibody responses were boosted by a second vaccination, whereas T-cell responses were not, isn’t completely surprising, said Scriba. This is because once a response is induced with the first vaccination, the immune response to that vaccination can, to some degree, neutralise the second vaccination.

“What this means is that the second vaccination isn’t quite as effective as the first, but that isn’t a bad thing.” Scriba added that the second dose is often given for two reasons:

“The first is to boost the initial immune response to get it a bit higher. The second reason is that it’s also important for those who don’t have a very good immune response to the first dose.

“It works out quite nicely in these people as they won’t end up having the type of immunity that neutralises the second dose.” This ultimately results in a higher proportion of the population that’s being vaccinated to develop an immune response.

“So it’s not that surprising that the Oxford University researchers saw a difference between the antibody and T-cell boosting, and it’s part of the general pattern, which makes it seem like this is going to be a successful vaccine,” commented Scriba.

T-cells not adequate to break chain of transmission 

Madhi also zeroed in on the importance of T-cell immunity during the ECN webinar:

“With seasonal coronaviruses, we do see persistence of T-cell immunity, which is a bit more long-lasting. But it does have implications because it might be that the T-cells are adequate to protect an individual from developing severe disease, but not actually adequate to break the chain of transmission.

“So, irrespective of whether you've got T-cell immunity or antibody, that does not mean that you’re not at risk of being reinfected. This happens with all respiratory viruses. The immune system does not protect you against infection – it protects you against developing disease.”

According to Madhi, the basic principle is that your first exposure to the pathogen would result in the most severe disease, and subsequent exposures would result in less severe disease. Madhi added that we need to guard against extrapolating information about immunity based on natural infection versus vaccination:

“Vaccination is done in a much more controlled manner, and we’re trying to enhance the immune response and do a better job than natural exposure [to the virus].”  

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