- After South Africa bought AstraZeneca vaccines from the Serum Institute of India, results from a small local study with only mild and moderate infections showed that the vaccine was not effective against the 501Y.V2 variant
- South Africa sold its AstraZeneca vaccines in March despite World Health Organisation (WHO) advice that the jab should still be used in countries where new variants are circulating
- Some experts, including the government’s ministerial advisory committee on vaccines, say the move is in line with South Africa’s evidence-based approach to Covid-19 decisions, while the Democratic Alliance and a group of scientists argue it’s a missed opportunity.
On 15 March, the health department sold a million doses of AstraZeneca vaccines, that arrived in South Africa in February, to the African Union. The government had procured the jabs from the Serum Institute of India in January.
The country’s vaccine roll-out had to pivot to the Johnson & Johnson vaccine before the first healthcare worker could be immunised. The reason: The ‘Covishield’ doses — Covishield is the name given to the AstraZeneca vaccine manufactured in India — were no match for the new variant dominating South Africa’s epidemic.
The decision went against the views of some researchers and marked a departure from the WHO’s guidance.
But some experts say the move is still in line with the country's evidence-based approach. We take a look back at everything we’ve learnt about the vaccine since then and break down exactly what happened to South Africa’s roll-out plans.
Why did we buy the AstraZeneca vaccine in the first place?
At the beginning of the year, following the peak of the country’s devastating second wave, Health Minister Zweli Mkhize announced that South Africa had secured 1.5-million doses of the Oxford/AstraZeneca COVID vaccine.
This decision came amidst growing public pressure for South Africa to begin its national vaccine roll-out, ahead of vaccine doses secured through the international procurement mechanism, COVAX.
At the time, a big factor being considered by the health department was which companies could deliver doses immediately, given the limited stock availability due to high global demand for the jabs, Health Minister Zweli Mkhize said during a televised address.
Another key component to choosing a vaccine is if it is safe and effective, and AstraZeneca was both, according to clinical trial data that was available at the time. But none of this information was from South Africa — the data showing the vaccine was 62.1% effective was from combined information from the United Kingdom and Brazil.
So what changed?
A month after the decision to procure AstraZeneca’s vaccine, on 7 February, new results from the local trial of the jab were released.
In a nutshell, the South African trial showed that the jab didn’t provide enough protection against mild to moderate Covid caused by the newly identified variant, Benjamin Kagina, a senior research officer at Vaccines for Africa Initiative explains.
The results from the study showed that AstraZeneca was only 21.9% effective against SARS-CoV-2 in South Africa. When researchers isolated those cases of participants who were infected with the new variant of the virus (B.1.351 or 501Y.V2) they noted that the jab was only 10.4% effective.
Further, laboratory studies confirmed that the variant was able to completely escape the vaccine’s immunity.
The WHO recommends using a Covid vaccine that offers at least 50% protection in a wide-scale roll-out.
On the basis of evidence: Is SA saying goodbye to AstraZeneca forever?
For now, the AstraZeneca jab has been placed on hold for South Africa’s roll-out. But this doesn’t necessarily mean that we’ll never consider it, says the chair of the ministerial advisory committee for Covid vaccines, Barry Schoub. Rather, it means that there isn’t yet enough evidence to support widespread use of the jab locally.
Kagina agrees: “Future studies could very well show that a booster shot given after the original jab could work well to protect people against mild and severe disease [caused by the new variant].”
Until more evidence is available, clear communication about what we do and don’t know about the vaccine will be key in maintaining the public’s trust in the jab, Kagina says.
AstraZeneca says the vaccine works well against severe disease in the United States, but all the data that supports this statement has not yet been released.
The complication, Schoub explains, is not the vaccine itself, but the variant currently dominating South Africa’s epidemic.
“The problem is this: The only evidence that we have got is negative.”
In a recent News24 op-ed, Schoub outlined where we stand. So here’s what we know:
- The AstraZeneca vaccine offers less protection than other jabs, such as those developed by Pfizer or Moderna for the common variants found elsewhere and the one developed by Johnson and Johnson for the dominant variant, 501Y.V2, in South Africa.
- Studies done in labs have shown that antibodies generated from the AstraZeneca jab often cannot kill the 501Y.V2 variant — this is not the case with other vaccines which have been tested.
- The South African arm of the AstraZeneca trial showed that the jab’s efficacy was reduced significantly in a local setting and only offered 10% protection against mild to moderate disease caused by the new variant.
But the South African study had limitations — it only included young people, who were unlikely to have fallen ill with severe disease; people above 60, who are much more likely to develop severe Covid, were excluded from the trial.
So it wasn’t so much that the data provided a clear path — instead, the lack of clear evidence was what ultimately informed the country’s decision.
A lingering question is: Can the vaccine prevent severe disease and reduce hospitalisations caused by the 501Y.V.2?
The answer remains unknown. This is in large part due to shortcomings in the local trial design.
The other important factor we need to consider is public trust in the vaccines.
Purchasing jabs for roll-outs is just one component of the process; making sure that people would want to take the vaccines is just as important.
To build trust in vaccines, there needs to be confidence in South Africa’s scientific bodies and medicine regulators, says Schoub. This means that there needs to be a trustworthy, scientific process behind recommending a jab.
He explains: “If at the end it transpires that the vaccine hasn’t worked after we’ve rolled out a million doses and a large number of people come down with severe disease, the public is going to lose trust in vaccines and our regulator’s ability to approve a safe and effective vaccine.
“We know we've got good vaccines, and the public needs to trust that we're saying that on the basis of scientific evidence.”
But some scientists in South Africa disagree. In an op-ed in the South African Medical Journal, they argue that rather than waiting for the “perfect jab” and focusing on public trust, the priority should be a fast vaccine roll-out (so we need to use the jabs we’ve got).
Moreover, they say the stop-start approach to the AstraZeneca vaccine in South Africa and in Europe (because of concerns that this vaccine is associated with blood clots) has already undermined trust in the jab and seen it labelled “second-best with reports of AstraZeneca-specific vaccine hesitancy from across the globe”.
What does the study actually tell us — and what don’t we know?
The South African AstraZeneca trial had four shortcomings, says Salim Abdool Karim, an infectious diseases epidemiologist and director of the Centre for the Aids Programme of Research in South Africa. Abdool Karim is also the former co-chair of the scientific ministerial advisory committee on Covid-19.
Let’s unpack the shortcomings a bit further.
1. The study wasn’t designed to measure protection against 501Y.V2
What’s more, unlike the other AstraZeneca trials, this local study was in the earlier stages of assessment and aimed to answer questions about the safety and protection the jab could offer people living with HIV.
“The study was designed and implemented around July, August, last year, before we even knew that there's a variant,” explains Abdool Karim. “So the study was designed for X and now that same study is being used to answer the question Y.”
The local trial was never attempting to answer how much protection the jab could offer against the 501Y.V2 variant, Kagina reiterates. Rather, this was something that came up in the findings as a result of the study’s timing.
But because it was never part of the original design, or a question that was being asked in the first place, it’s hard to draw definite conclusions because the data just isn’t there.
2. There were too few people in the study
The study included a little over 2 000 people, which is typically the number of participants you would expect in an early clinical trial.
To make firm decisions about a vaccine in a late-stage clinical trial, a larger group of participants — of between 40 000 to 50 000 — would be preferable, cautions Abdool Karim. The more people involved in a study, the greater the data available, especially for uncommon events such as severe Covid-19, and that makes it easier to draw statistically significant conclusions from the study.
In small trials, as in the case of the South African AstraZeneca trial, there are likely to be less symptomatic Covid cases, Andy Gray, a pharmacology lecturer at the University of KwaZulu-Natal, told Bhekisisa earlier this year.
3. The trial didn’t include any old people
The study primarily included younger people, with most aged around 30 years old. But a key part of South Africa’s roll-out targets people over the age of 60 and those who are at increased risk of developing severe disease because of comorbidities such as obesity or diabetes.
Because the South African trial tested the vaccine in a largely young and healthy population, it can’t answer crucial questions such as how the vaccine performs in older people, whether it reduces severe disease or whether it can prevent hospitalisations.
4. The recommended dosing interval changed
The AstraZeneca vaccine is given in two doses — these doses were initially designed to be given 28 days apart.
But, at the beginning of February, after further testing, researchers recommended that the doses be given further apart as this improves the protection offered.
In other words, the South African trial’s design had already become outdated before it was completed because it was not using the optimal dosing regimen.
“They gave AstraZeneca doses 28 days apart,” explains Abdool Karim. “The AstraZeneca team has shown that 28 days apart is not very effective and instead you've got to give the doses about 80-120 days apart to get higher efficacy. So the study actually used a dosing interval that AstraZeneca is not recommending anymore.”
The WHO has since recommended that the doses be administered with an interval of eight to 12 weeks between the shots.
Should South Africa have sold its doses?
South Africa completed the sale of its AstraZeneca doses on 15 March, a few weeks after a WHO expert group concluded that the “potential benefits [of the AstraZeneca vaccine] outweigh the known and potential risks”.
The WHO recommends the use of the vaccine even in countries such as South Africa where new variants are in circulation for which the jab has shown reduced efficacy.
“[The WHO] is simply saying go with it, because we think it's still going to work. It's a speculation,” explains Schoub. “There’s no evidence.”
He says: “We've always been based on interventions on science and I don't think we should actually make an exception now.”
Abdool Karim echoed this in a reflection he did on the one year anniversary of South Africa’s first Covid case. “I am very hesitant that we would give a million doses based on speculation. I would like to have a little bit of evidence, especially on severe disease because there is this concern that it doesn’t protect against mild disease.”
He explained that this evidence would ordinarily be expected to be provided by AstraZeneca for their vaccine.
It also would have been wasteful to just continue storing the vaccines in South Africa, explains Schoub.
At that stage, the expiry date printed on the boxes of the vaccines indicated they were going to expire in April. Although according to Schoub, the expiry date has since been extended for another three months by the Serum Institute of India, it still would have meant that we were dealing with something that had a limited lifespan.
Schoub says: “The department of health took the decision to rather sell the vaccine, where it could be used very profitably in countries which either don’t have the variant or where the variant is very minor.”
Rather than trying to experiment with the vaccine and seeing what does or doesn’t work, Schoub believes that it was better for South Africa to focus on getting other jabs into the country and devoting available resources to vaccinating as many people as possible.
But other scientists disagree: “We believe that SA has squandered the opportunity to protect at least half a million of its most vulnerable citizens before the next resurgence, with massive healthcare and economic cost.
"Alternatives to the AZ vaccine will not be available to South Africans within the next few months to make up the shortfall,” write authors for an opinion piece published in the South African Medical Journal.
Why didn’t South Africa continue testing the AstraZeneca jab?
We’re doing an implementation study to assess the Johnson & Johnson vaccine in the country, so couldn’t we do the same thing with the AstraZeneca jab?
According to Abdool Karim, the answer is no.
This is because time is of the essence, he says, and testing the doses we had wouldn’t have been worth it.
Remember how the AstraZeneca researchers recommended a dosing interval of three months between the two shots? That becomes important when considering doing further studies of the jab.
Unlike the other Covid vaccines currently available, Johnson & Johnson’s jab requires just one dose. That makes it easier to roll-out and continue assessing through an implementation study.
AstraZeneca, on the other hand, would need a two to three month lead time between injections. This means we could only start gathering information from the study six to eight months down the line and that would be too late to make a trial that assesses whether the jab can prevent severe diseases worthwhile, says Abdool Karim.
Why? Because by then, there will likely be a second generation of the AstraZeneca vaccine designed specifically for the new variant, Abdool Karim says.
He says you first have to ask: “Is testing the AstraZeneca vaccine with a result only being available in late 2021, something that would be meaningful?”
“The answer is no. Because at that stage we don’t know what new variants would have come about and where we would be. So we’re basically going to do a study and commit a huge amount of resources to research for which the answer it’s not going to be meaningful [because the research results came too late].
What’s in a vector anyway?
The AstraZeneca jab is a viral vector vaccine. This means it uses a vector — a harmless version of a virus — as a sort of ‘trojan horse’ to sneak in a part of the coronavirus (in this case the spike protein). By hiding the coronavirus in this way, the vaccine can safely prime your body to protect itself against SARS-CoV-2.
But there are concerns that come with the type of vector used in the AstraZeneca vaccine — a chimp adenovirus.
Abdool Karim says that previous studies into a possible vaccine for HIV using the same type of vector had unexpected negative effects on participants — increasing some participants' risk of HIV.
The risk with viral vector vaccines that use an adenovirus, he says, is that your body could react to the vector.
For instance, a Merck HIV vaccine study using adenovirus type-5 found that the risk of HIV infection increased in participants with pre-existing natural immunity to the vector when they received the vaccine.
This has led to a concern about using the same adenovirus vector multiple times as initial doses would create pre-existing immunity for subsequent doses, which may run the risk of a similar effect on HIV risk.
Abdool Karim, however, noted that this risk has not yet been studied or quantified for chimp adenovirus vectors and so it is not yet known if this is a concern. On the other hand, the adenovirus type-26 vector, which is used in the Johnson & Johnson jab, as well as one of the Gamaleya vaccines from Russia, has been shown to be safe in studies using adenovirus type-26 for HIV vaccines.
“We do not want to put ourselves in a position where we’re doing one thing and inadvertently causing another problem,” Abdool Karim said about the AstraZeneca vaccine.
“We can’t just do things and then we might do harm and then say, oh, we should have thought of that. Let’s think of it first, let’s collect the evidence and then based on the evidence we act.”