Can the world learn from vaccine trials in South Africa?

In a year that has oscillated between astonishing gains and brutal setbacks on Covid-19, a few moments have been as disappointing as the revelation last month that a variant of the coronavirus in South Africa was mitigating the effect of one of the most powerful vaccines in the world.

This discovery – from a South African trial of the Oxford-AstraZeneca vaccine – revealed how quickly the virus had managed to dodge human antibodies, ending what some researchers have described as the global honeymoon period with the Covid-19 vaccines and lowering hopes of containing the virus. pandemic.

As countries adjust to this unsettling twist of fortune, the story of how scientists discovered the dangers of the variant in South Africa has shed light on global vaccine trials that were needed to warn the world .

“Historically, people would have thought that a problem in a country like South Africa would stay in South Africa,” said Mark Feinberg, managing director of IAVI, a nonprofit scientific research group. “But we’ve seen how quickly variants are popping up all over the world. Even rich countries need to pay a lot of attention to the changing landscape all over the world. “

Once thought through in the vaccine race, these global trials saved the world from sleepwalking in the second year of the coronavirus, oblivious to how the pathogen might blunt the body’s immune response, scientists have said. They also hold lessons on how vaccine makers can tackle new variants this year and correct long-standing health inequalities.

The platform is often opposed to drug trials in poorer countries: drug and vaccine makers look to their largest commercial markets, often avoiding the expense and uncertainty of product testing in the south of the country. planet. Less than 3 percent of clinical trials take place 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 did before, before testing whether injections made for countries rich also operate in the poorest countries.

“If you don’t identify and react to what’s going on in a supposedly remote continent, it has a significant impact on global health,” said Clare Cutland, vaccine specialist at the University of the Witwatersrand in Johannesburg, who coordinated the Oxford trial. “These results showed the world that we are not dealing with a single pathogen that just stands there and does nothing – it is constantly changing.”

Although it offers minimal protection against mild to moderate cases caused by the variant in South Africa, the Oxford vaccine will likely prevent these patients from becoming seriously ill, preventing a surge in hospitalizations and death. Laboratory studies have generated a mix of encouraging and more disturbing results on the extent to which the variant interferes with the shots from Pfizer and Moderna.

Still, vaccine makers are rushing to test updated booster shots. And countries are trying to isolate cases of the variant, which South African trials show may also be able to re-infect people.

Last March, long before scientists worried about variants, Shabir Madhi, a veteran vaccine specialist at the University of the Witwatersrand, began pressuring vaccine makers to let him do trials.

Realizing how long Africa often waits for life-saving vaccines, as it did for swine flu vaccines ten years ago, Dr Madhi wanted to quickly study how Covid-19 vaccines worked on the continent, including in people living with HIV. He hoped that would leave the world no excuse to delay approvals or procurements. Different socio-economic and health conditions can affect vaccine performance.

“I’m sure I can get funding,” he emailed the Oxford team on March 31 last year, adding that “it would be important to assess in context HIV “

Oxford agreed and the Bill and Melinda Gates Foundation contributed $ 7.3 million, further strengthening its role as a hub in efforts to orient vaccine trials to the south of the globe.

Nonetheless, the trial faced challenges that larger, better-resourced studies in the United States and Europe did not. On the one hand, Dr Madhi’s team had to eliminate several test sites because they did not have sufficiently cold back-up freezers or generators, a necessity in a country where frequent power cuts could jeopardize precious doses.

Even after the researchers locked the sites down, relying on clinics experienced in conducting studies on HIV, the trial was nearly called off. Test results showed that nearly half of the first volunteers were already infected with the virus by the time they were vaccinated, reversing their results.

“We had a limited amount of funding and a limited number of vaccines,” said Dr. Cutland. “We were very concerned about the total derailment of the trial.”

At another test site, the three pharmacists contracted Covid-19, ruling out the only people authorized to prepare injections. Nurses participating in the trial lost their siblings and parents to the disease. Staff were so overwhelmed that when vaccine officials called from overseas, phones rang and sometimes rang.

The force of the pandemic in South Africa – 51,000 people have died and up to half of the population may have been infected – nearly overturned the lawsuit. But it was also part of what attracted vaccine makers: More cases means faster results.

Dr Madhi’s team weathered the storm, working 12 hours a day and adding last-minute swabs to make sure volunteers weren’t already infected. In May, he asked Novavax, then a little-known American company with backing from the Trump administration, to conduct a trial there as well. Novavax agreed and the Gates Foundation invested $ 15 million. But the trial was not registered until a few months later.

Novavax said the trial took a long time to come together. But the delay also reflected what scientists described as pressure on US-backed vaccine makers to focus their efforts in the United States. Studies on this topic are the best way to get the coveted approvals from the Food and Drug Administration, the world’s leading drug agency.

And vaccine manufacturers tend to know their larger markets better.

“Companies have the most experience with clinical trials in regions of the world that represent their commercial markets,” said Dr Feinberg.

For vaccine makers who have made sourcing the world a centerpiece of their strategies, the trials have been a godsend. Novavax showed that its vaccine efficacy was only moderately weakened by the variant in South Africa. Johnson & Johnson, who also conducted a South African trial, have shown that their vaccine protects against hospitalization and death in that country.

“You have your fishing line in the water – and while we were there the virus evolved,” said Dr Gregory Glenn, president of research and development at Novavax. “This is invaluable data for us and for the world.”

In a recent laboratory study, the Oxford-AstraZeneca vaccine protected hamsters exposed to the variant against the disease, even though the animals’ immune responses were somewhat weaker. The human trial in South Africa was too small to definitively say whether the vaccine prevented serious disease. But the finding that it offered minimal protection against the mildest cases was in itself disheartening, given that shooting remains the backbone of deployments in many poorer countries.

In South Africa, the results sabotaged plans to give the Oxford vaccine to health workers. Despite hosting trials, the country has failed to leverage it to secure advance purchase agreements, delaying supplies. Only a fifth of 1 percent of people have been vaccinated there, raising fears of a new wave of deaths and new mutations.

While HIV research laid the groundwork for vaccine trials in South Africa, some scientists are hoping that an explosion of global pandemic studies will show drug companies that other countries also have the infrastructure to conduct major testing.

To that end, the Coalition for Epidemic Preparedness Innovations, a group backed by Gates, is encouraging companies to organize further Covid-19 vaccine trials in poorer countries.

“People tend to go for what they know,” said Melanie Saville, director of vaccine research and development for the coalition. “But the capacity is increasing in low- and middle-income countries, and we need to encourage developers to use it.”

South Africans volunteered for the trials in large numbers. Most mornings, Dr Anthonet Koen, who ran a Johannesburg site for the Oxford and Novavax trials, opened at 6 a.m., when participants had already been queuing outside for two hours.

On December 11, Dr Koen noticed that the pandemic had escalated: After weeks without cases, two people in the trial tested positive. Then more and more, every day. Health officials announced the discovery of the variant a week later. The fortuitous placement of the trials gave scientists what they almost never have: an open-air laboratory to observe, in real time, a vaccine and a variant face-to-face.

Since the Oxford results were announced last month, Dr Koen said, volunteers have tried to console her: “I get a lot of condolence messages and I’m sorry,” she said.

As long as this vaccine and others prevent serious illness, even in cases of the variant, the world can live with the virus, scientists have said. But the trial in South Africa nonetheless underscored the need to eradicate the virus before it mutates further. Without it, the scientists said, the world could have been blind to what was to come.

“We predict that these variants are not the end of the story,” said Andrew Pollard, the Oxford scientist in charge of his trials. “In order for the virus to survive, once populations have good immunity to the current variants, it must continue to mutate.”