CAPE TOWN – The failure of the Oxford/ AstraZeneca SARS-COV2 vaccine to protect against the COVID-19 variant identified in South Africa has serious implications for massive African vaccine rollouts planned by both the WHO co-sponsored COVAX vaccine facility as well as the African Union’s dedicated African Vaccine Acquisition Task Team (AVATT).

The bulk of Africa’s COVAX allocations and a significant proportion of the AVATT acquisitions are for the AstraZeneca vaccine produced by the Serum Institute of India (SII).  Yet most southern African countries neighboring South Africa are almost certain to be dominated by the B.1.351 variant  (also called 501Y-V2) which was first identified in South Africa. The variant has already appeared in Malawi, eSwatini, Lesotho, Mozambique, Zambia and Zimbabwe, experts say, and it could have already spread to East Africa.

South Africa’s health minister, Dr Zweli Mkhize told a media briefing on Sunday night that the country had suspended its planned rollout of the AstraZeneca vaccine – due to the failure of a recent South African trial to show that the vaccine was effective against preventing mild to moderate disease from the B.1.351 variant. The decision came just one week after one million AstraZeneca doses had arrived in the country as a result of a bilateral deal with SII.

The country now plans to vaccinate its health workers with the Pfizer vaccine, which it will get via COVAX. It is also in negotiations with Johnson & Johnson to purchase its vaccine, which has shown reduced efficacy against the 501Y-V2 variant but was 85% effective in reducing serious illness, although it is not yet approved by the country’s regulator.

Officials also are considering rolling out the AstraZeneca vaccine to 100,000 people and monitoring hospitalisations – to see if the vaccine may still be more effective in reducing serious disease.

“If we are confident that the vaccine is effective in preventing hospitalisation, then we can roll it out,” said South Africa’s co-chair of the Ministerial Advisory Committee on COVID-19, Professor Salim Abdool Karim. “Alternatively, if it’s above that threshold, then we need to look at alternatives.

“So put very simply. We don’t want to end up with a situation where we vaccinated, a million people, or too many people with a vaccine, that may not be effective in preventing hospitalisation and severe disease.”

Vaccine Study Inadvertently Tested Efficacy on Variant

At a media briefing on Monday, Professor Shabir Madhi, principal investigator on the South African arm of a Phase 2 trial on the two-dose AstraZeneca vaccine, the progress of the trial and its findings, which included 1750 largely young and healthy participants. 

Initially, the vaccine showed 75% efficacy at 14 days, but as the trial progressed – and the majority of participants who became infected by the variant – this protective plummeted until it was “not statistically significant”, said Madhi.

“Inadvertently, because of the timing of when we enrolled participants into the study, 95% of all of the individuals infected after two doses, were infected as a result of the variant, so this study was able to show the vaccine’s efficacy on the variant” said Madhi.

Of the 42 people who contracted the virus, 23 were in the placebo arm and 19 in the vaccine arm. 

“What data doesn’t tell us is whether or not this vaccine might still protect against severe COVID-19, as two thirds of those infected had mild symptoms and a third had moderate symptoms,”, said Madhi. 

It remains possible that the AstraZeneca vaccine may offer protection against severe illness, insofar as it uses the same viral vector technology as the Johnson & Johnson vaccine, which was found to be 85% effective at reducing severe illness and death in a recent Phase 3 trial.

The J&J study involved over 44,000 people, a third of whom were over the age of 60. Overall, it showed 72% efficacy against the virus in the US but only 57% efficacy rate in South Africa because of the B.1.351 variant, reported Dr Glenda Gray, head of the SA Medical Research Council who ran the South African arm of the study.

Gray said that, given J&J’s proven efficacy in protecting against severe illness and death, she would be expanding her study to health workers within the next few days while waiting for it to be approved in the country.

Meanwhile, AstraZeneca and Oxford University are already developing a booster shot based on the locally-identified variant. 

“Efforts are underway to develop a new generation of vaccines that will allow protection to be redirected to emerging variants as booster jabs, if it turns out that it is necessary to do so,” said Sarah Gilbert, Professor of Vaccinology at the University of Oxford in a press release.

“We are working with AstraZeneca to optimise the pipeline required for a strain change should one become necessary. This is the same issue that is faced by all of the vaccine developers, and we will continue to monitor the emergence of new variants that arise in readiness for a future strain change.”

Professor Barry Schoub, co-chair of the South African Ministerial Advisory Committee on COVID-19 vaccines, described the AstraZeneca results as “rather disappointing”, but said there may be a way to salvage the vaccine.

“For example, we need to look at the cell mediated immune responses; we may need to look at a combination of AZ vaccine with other vaccines which may in fact give a synergistically good response. So I just think we need to maybe suspend use of AstraZeneca, but investigate more fully [if we] can utilise it more effectively,” Schoub told the Sunday media briefing.

Meanwhile, Mkhize said that the country needed to figure out its next step in regard to the vaccine, which it paid more than twice the price that the European Union did, with the guidance of scientists.

Novavax and Moderna have also shown decreased efficacy against the 501Y-V2 variant. 

Australia’s Minister for Health, Greg Hunt, said on Monday that “there is currently no evidence to indicate a reduction in the effectiveness of either the AstraZeneca or Pfizer vaccines in preventing severe disease and death.”

Australia is on the brink of approving the AstraZeneca vaccine and has ordered 53 million doses, largely relying on the Oxford/AstraZeneca vaccine to inoculate the whole population. But the 501Y-V2 variant has already spread to at least 32 countries, including Australia. 

WHO’s Strategic Advisory Group of Experts on Immunization (SAGE) was meeting on Monday to review AstraZeneca’s clinical trial results and propose recommendations to WHO on the provision of Emergency Use Listing to the vaccine. 

This setback for AstraZeneca is on top of the decision by several European countries last week to implement an age restriction for the vaccine due to a lack of efficacy data in people over the age of 65 and Switzerland’s rejection of AstraZeneca’s application for regulatory approval until more data is received. 

WHO Director General Dr Tedros Adhanom Ghebreyesus at the body’s biweekly press briefing. on Monday: “Yesterday, South Africa announced that it was putting a temporary hold on the rollout of the Oxford AstraZeneca vaccine. After a study showed it was minimally effective at preventing mild to moderate disease caused by a variant first identified in South Africa.

“This is clearly concerning news. However, there are some important caveats, given the limited sample size of the trial, and the younger healthier profile of the participants. It’s important to determine whether or not the vaccine remains effective in preventing more severe illness.”