SA AstraZeneca study was a downer, but pointed way ahead, says Madhi

SA hasn't yet administered a single Covid-19 vaccine outside clinical trials, but research carried out in the country has made a “compelling case” for the development of second-generation vaccines.

“The findings of our [Oxford/AstraZeneca Covid-19 vaccine] study are truly a turning point in Covid-19 vaccine development — and a rude awakening,” said Prof Shabir Madhi, who led a trial with more than 2,000 participants.

“This one, small South African study has alerted the world to the fact that second-generation Covid-19 vaccines will be required to provide protection against inevitable and persistent SARS-CoV-2 variants,” said the head of the vaccines and infectious diseases analytics research unit at Johannesburg's Wits university.

“If we had not conducted this trial in SA, the world would be none the wiser.”

The study, published on Tuesday in the New England Journal of Medicine, found the AstraZeneca vaccine does not have efficacy of at least 60% against mild-moderate Covid-19 due to the B. 1.351 (N501Y. V2) variant, first identified in the Eastern Cape and now the dominant strain circulating in SA.

Based on this finding, SA shelved its AstraZeneca vaccines and hopes to sell them to the AU.

However, based on a broader body of evidence, the World Health Organisation (WHO) recommends using the vaccine in countries where the B. 1.351 variant circulates, as it probably still protects against severe infection, hospitalisation and death.

Madhi, who has been a vocal supporter of the WHO approach, said: “Despite the disappointing finding that the AstraZeneca vaccine did not protect against mild Covid-19 infection because of the B. 1.351 variant first identified in SA, peer review and publication of our research validates the findings and makes a compelling case for the development of a second-generation vaccines worldwide.”

First-generation vaccines refer to those designed to respond to the original SARS-CoV-2 virus. Second-generation vaccines involve technology and design innovations that can provide protection against the constantly evolving variants that cause Covid-19.

The findings of Madhi's team were publicised as a preprint early in February, less than a week after SA took delivery of a million doses of the Oxford/AstraZeneca vaccine.

“We were in a state of euphoria about the high efficacy of several Covid-19 vaccines against the original virus, but then the AstraZeneca study threw us a curve ball,” said Madhi.

The randomised, multi-centre, double-blinded trial enrolled 2,026 participants between June and November 2020. Most were under the age of 65, generally healthy and HIV-negative. The median age was 30, 56.5% were men, 70.5% were black, 12.8% white and 14.9% coloured.

“These demographics are important because they reflect characteristics of the overall population in SA. Conducting clinical trials in diverse settings like these is critical to understanding how vaccines work in local contexts,” said Madhi.

“A trial enrolling just 2,026 participants is considered small, while phase three trials enrol tens of thousands of participants. Yet the startling data that [it] generated was irrefutable  and the implications profound.

“When this trial began in June 2020, we were testing a vaccine against SARS-CoV-2. By January 2021, SARS-CoV-2 had spawned variants, including the B. 1.351 first discovered in SA.

“As a secondary objective we tested a hypothesis: would this vaccine prove at least 60% efficacious in preventing mild to moderate Covid-19 disease? It did not.

“This vaccine may still help protect high-risk individuals with comorbidities from contracting severe Covid-19 disease, having to be hospitalised, mechanically ventilated or dying.

“The AstraZeneca vaccine remains essential in the arsenal against this virus, particularly in Africa, which has already received 14 million doses of this vaccine as the Covid-19 immunisation programme starts in multiple countries.”