Can the world learn from South Africa’s vaccine trials?

In a year that has seesawed between astonishing gains and brutal setbacks on COVID-19, few moments were as sobering as the revelation last month that a coronavirus variant in South Africa was dampening the effect of one of the world’s most potent vaccines.

That finding — from a South African trial of the Oxford-AstraZeneca shot — exposed how quickly the virus had managed to dodge human antibodies, ending what some researchers have described as the world’s honeymoon period with COVID-19 vaccines and setting back hopes for containing the pandemic.

As countries adjust to that jarring turn of fortune, the story of how scientists uncovered the dangers of the variant in South Africa has put a spotlight on the global vaccine trials that were indispensable in warning the world.

“Historically, people might have thought a problem in a country like South Africa would stay in South Africa,” said Mark Feinberg, chief executive of IAVI, a nonprofit scientific research group. “But we’ve seen how quickly variants are cropping up all around the world. Even wealthy countries have to pay a lot of attention to the evolving landscape all around the world.”

Once afterthoughts in the vaccine race, those global trials have saved the world from sleepwalking into year two of the coronavirus, oblivious to the way the pathogen could blunt the body’s immune response, scientists said. They also hold lessons about how vaccine makers can fight new variants this year and redress longstanding health inequities.

The deck is often stacked against medicine trials in poorer countries; drug and vaccine makers gravitate to their biggest commercial markets, often avoiding the expense and the uncertainty of testing products in the global south. Under 3% of clinical trials occur in Africa.

Yet the emergence of new variants in South Africa and Brazil has shown that vaccine makers cannot afford to wait years, as they often used to, before testing whether shots made for rich countries work in poorer ones, too.

“If you don’t identify and react to what’s happening in some supposedly far-flung continent, it significantly impacts global health,” said Clare Cutland, a vaccine scientist at the University of the Witwatersrand in Johannesburg, who coordinated the Oxford trial. “These results highlighted to the world that we’re not dealing with a single pathogen that sits there and does nothing; it’s constantly mutating.”

Despite offering minimal protection against mild or moderate cases caused by the variant in South Africa, the Oxford vaccine is likely to keep those patients from becoming severely ill, averting a surge of hospitalizations and deaths. Lab studies have generated a mix of hopeful and more worrisome results about how much the variant interferes with Pfizer’s and Moderna’s shots.

Nevertheless, vaccine makers are racing to test updated booster shots. And countries are trying to isolate cases of the variant, which the South African trials showed also may be able to reinfect people.

Last March, long before scientists were fretting about variants, Shabir Madhi, a veteran vaccinologist at the University of the Witwatersrand, began lobbying vaccine makers to let him run trials.

Aware of how long Africa often waits for lifesaving vaccines, as it did for swine flu shots a decade ago, Madhi wanted to quickly study how COVID-19 vaccines worked on the continent, including in people with HIV. He hoped that would leave the world no excuse for delaying approvals or supplies. Different socioeconomic and health conditions can change vaccines’ performance.

“Am sure I can get funding,” he emailed the Oxford team March 31 last year, adding that it “would be important to evaluate in context of HIV.”

Oxford agreed, and the Bill and Melinda Gates Foundation contributed $7.3 million, cementing its role as a linchpin of efforts to steer vaccine trials to the global south.

Nevertheless, the trial had to contend with difficulties that bigger, better-resourced studies in the United States and Europe did not. For one thing, Madhi’s team had to eliminate several trial sites because it did not have cold enough freezers or backup generators, a necessity in a country where frequent power outages could imperil precious doses.

Even once the researchers locked down sites, relying on clinics with experience running HIV studies, the trial nearly came undone.

Test results showed that nearly half the earliest volunteers already were infected with the virus at the time they were vaccinated, voiding their results.

The force of the pandemic in South Africa — 51,000 people have died, and up to half the population may have been infected — nearly toppled the trial.

But that was also part of what drew vaccine makers: More cases mean faster results.

Madhi’s team weathered the storm, working 12-hour days and adding last-minute swabs to ensure that volunteers were not already infected.