In a year that oscillated between surprising gains and brutal setbacks at Covid-19, few moments were as worrying as last month’s revelation that a variant of the coronavirus in South Africa was lessening the effect of one of the most potent vaccines in the world.
This discovery – from a trial in South Africa with the Oxford-AstraZeneca injection – exposed how quickly the virus managed to evade human antibodies, ending what some researchers described as the world’s honeymoon period with Covid vaccines. -19 and lowering hopes of containing the pandemic.
As countries adjust to this shocking change in fortune, the story of how scientists discovered the dangers of the variant in South Africa put the spotlight on the global vaccine tests that were indispensable to alert the world.
“Historically, people may have thought that a problem in a country like South Africa would remain in South Africa,” said Mark Feinberg, chief executive of IAVI, a nonprofit scientific research group. “But we have seen how variants are emerging rapidly around the world. Even rich countries need to pay close attention to the evolving landscape around the world. “
After further reflection in the vaccine race, these global tests saved the world from sleepwalking in the second year of the coronavirus, oblivious to how the pathogen can weaken the body’s immune response, the scientists said. They also offer lessons on how vaccine manufacturers can tackle new variants this year and address long-standing health inequalities.
The deck is often against drug testing in poorer countries: drug and vaccine manufacturers gravitate to their largest commercial markets, often avoiding the expense and uncertainty of testing products in the global south. Less than 3 percent of clinical trials are conducted in Africa.
However, the emergence of new variants in South Africa and Brazil has shown that vaccine manufacturers cannot afford to wait years, as they used to, before testing whether vaccines made for rich countries work in the poorest as well. .
“If you don’t identify and react to what is happening on some supposedly distant continent, it will have a significant impact on global health,” said Clare Cutland, a vaccine scientist at the University of Witwatersrand in Johannesburg, who coordinated the Oxford study. “These results have highlighted to the world that we are not dealing with a single pathogen that stands still and does nothing – it is constantly changing.”
Despite offering minimal protection against mild or moderate cases caused by the variant in South Africa, the Oxford vaccine is likely to prevent these patients from becoming seriously ill, preventing an increase in hospitalizations and deaths. Laboratory studies have generated a mixture of hopeful and more worrying results about how much the variant interferes with Pfizer and Moderna photos.
However, vaccine manufacturers are rushing to test updated booster shots. And countries are trying to isolate cases of the variant, which South African tests have shown that it may also be able to reinfect people.
Last March, long before scientists were concerned about the variants, Shabir Madhi, a veteran vaccinologist at the University of Witwatersrand, began lobbying vaccine manufacturers to let him run tests.
Aware of how long Africa often waits for life-saving vaccines, as he did for swine flu vaccines a decade ago, Dr. 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 with no excuse for delaying approvals or supplies. Different socioeconomic and health conditions can alter the performance of vaccines.
“I’m sure I can get funding,” he sent an email to the Oxford team on March 31 last year, adding that “it would be important to assess in the context of HIV”
Oxford agreed, and the Bill and Melinda Gates Foundation contributed $ 7.3 million, consolidating its role as a pillar of efforts to conduct vaccine testing for the global south.
However, the test had to face difficulties 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 didn’t have cold enough freezers or backup generators, a necessity in a country where frequent power outages could endanger precious doses.
Even after the researchers closed the sites, relying on clinics with experience in HIV studies, the test was almost undone. The test results showed that almost half of the first volunteers were already infected with the virus by the time they were vaccinated, nullifying their results.
“We had limited funding and a limited number of vaccines,” said Cutland. “We were very concerned about the total derailment of the trial.”
At another test site, the three pharmacists hired Covid-19, setting aside the only people allowed to prepare injections. Nurses in the study lost siblings and parents to the disease. The team was so overloaded that when vaccine executives called from abroad, the phones sometimes rang and rang.
The strength of the pandemic in South Africa – 51,000 people died and up to half the population may have been infected – has almost brought the trial down. But that was also part of what attracted vaccine manufacturers: more cases mean faster results.
Dr. Madhi’s team withstood the storm, working 12 hours a day and adding last-minute swabs to make sure the volunteers were no longer infected. In May, he asked Novavax, then a little-known American company with support from the Trump administration, to do a test there as well. Novavax agreed, and the Gates Foundation raised $ 15 million. But the trial was registered just a few months later.
Novavax said the trial took too long to be carried out. But the delay also reflected what scientists described as pressure on American-backed vaccine manufacturers to focus their efforts in the United States. Studies show the best way to unlock coveted approvals from the Food and Drug Administration, the global gold standard drug agency.
And vaccine manufacturers tend to know their biggest markets better.
“Companies are more experienced in conducting clinical trials in parts of the world that represent their commercial markets,” said Dr. Feinberg.
For vaccine manufacturers who have made supplying the world a centerpiece of their strategies, the tests have been a blessing. Novavax showed that its vaccine effectiveness was only moderately weakened by the variant in South Africa. Johnson & Johnson, which also ran a trial in South Africa, showed that its vaccine protected against hospitalization and death in that country.
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“You have your fishing line in the water – and in the time we were there, the virus has evolved,” said Dr. Gregory Glenn, president of research and development at Novavax. “This data is invaluable for us and the world.”
In a recent laboratory study, the Oxford-AstraZeneca vaccine protected hamsters exposed to the variant from falling ill, even though the animals’ immune responses were slightly weaker. The human test in South Africa was too small to say definitively whether the vaccine prevented serious illnesses. But the discovery that it provided minimal protection against milder cases was in itself disheartening, as the shot remains the backbone of implementations in many poorer countries.
In South Africa, the results hampered plans to give the Oxford vaccine to healthcare professionals. Despite hosting the tests, the country was unable to make advance purchase agreements, delaying supply. Only a fifth of 1 percent of the people there were vaccinated, raising fears of another wave of deaths and new mutations.
If HIV research laid the groundwork for vaccine testing in South Africa, some scientists hope that an explosion of global pandemic studies will demonstrate to pharmaceutical companies that other countries also have the infrastructure to carry out major tests.
To that end, the Coalition for Epidemic Preparedness Innovations, a group supported by Gates, is encouraging companies to conduct more Covid-19 vaccine tests in poorer countries.
“People tend to look for what they know,” said Melanie Saville, the coalition’s director of vaccine research and development. “But capacity is increasing in low and middle-income countries and we need to encourage developers to use it.”
South Africans volunteered for the tests in large numbers. Most mornings, Dr. Anthonet Koen, who ran a website in Johannesburg for the Oxford and Novavax trials, opened its doors at 6 am, when participants were already lining up outside for two hours.
On December 11, Dr. Koen noticed that the pandemic was increasing: after weeks without a case, two people in the study tested positive. So, more and more, every day. Health officials announced the discovery of the variant a week later. The random location of the tests gave scientists what they almost never have: an open-air laboratory to watch, in real time, how a vaccine and a variant face each other.
Since the results of Oxford were announced last month, Koen said, the volunteers have been trying to comfort her: “I’m getting a lot of messages of condolence and ‘I’m sorry,'” she said.
While this vaccine and others prevent serious diseases, even in cases of the variant, the world can live with the virus, the scientists said. But the test in South Africa underscored the need to eradicate the virus before it mutates further. Without it, scientists said, the world could have been blind to what was to come.
“We anticipate that these variants are not the end of the story,” said Andrew Pollard, the Oxford scientist responsible for his tests. “For the virus to survive, once populations have good immunity against current variants, it must continue to undergo mutations.”