In a Essential South African Vaccine Trial, a Cautionary Story
In a year that has fluctuated between staggering profits and brutal setbacks at Covid-19, few moments have been as sobering as last month’s discovery that a variant of coronavirus in South Africa was dampening the effects of one of the most effective vaccines in the world.
That finding – from a South African trial with the Oxford-AstraZeneca shot – revealed how quickly the virus had managed to evade human antibodies, ending what some researchers have described as the worldwide honeymoon period with Covid-19 vaccines, and continuing that Hopes return to contain the pandemic.
As countries prepare for this difficult turnaround, the story of how scientists uncovered the dangers of the variant in South Africa has brought focus to global vaccine trials, which were essential in warning the world.
“Historically, people might have thought that a problem in a country like South Africa would remain in South Africa,” said Mark Feinberg, executive director of IAVI, a nonprofit scientific research group. “But we’ve seen how quickly variants pop up all over the world. Even wealthy countries need to pay a lot of attention to the developing landscape around the world. “
After the deliberations in the vaccine race, these global studies saved the world from sleepwalking into the second year of the coronavirus without knowing how the pathogen might weaken the body’s immune response, scientists said. They also give lessons on how vaccine manufacturers can combat new variants and eliminate long-standing health inequalities this year.
The deck is often stacked against drug trials in poorer countries: drug and vaccine manufacturers attract their largest commercial markets, and often avoid the cost 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 varieties in South Africa and Brazil has shown that vaccine manufacturers cannot afford to wait years, as they often have, before testing that shots work for rich countries in poorer ones.
“If you fail to recognize and react to what is happening on a seemingly distant continent, it has a significant impact on global health,” said Clare Cutland, a vaccine scientist at the Witwatersrand University in Johannesburg who coordinated the Oxford study. “These results have shown the world that there isn’t a single pathogen sitting there doing nothing – it is constantly mutating.”
Although the Oxford vaccine offers minimal protection against mild or moderate cases caused by the variant in South Africa, it will likely prevent these patients from becoming seriously ill, preventing an increase in hospitalizations and deaths. Laboratory studies have produced a mix of hopeful and more worrying results about how much the variant disrupts Pfizer and Moderna’s recordings.
Even so, vaccine manufacturers are trying to test updated booster vaccinations. And countries are trying to isolate cases of the variant that South African studies have shown could potentially re-infect humans as well.
In March of last year, long before scientists became angry about variants, Shabir Madhi, a veteran vaccinologist at the Witwatersrand University, began to persuade vaccine manufacturers to conduct trials.
Dr. Realizing how long Africa often waits for life-saving vaccines, as it did with swine flu vaccinations a decade ago, Madhi wanted to quickly examine how Covid-19 vaccines work on the continent, even for people with HIV the world no excuse for the delay in permits or deliveries. Different socio-economic and health conditions can change the performance of vaccines.
“I’m sure I can get money,” he emailed the Oxford team on March 31 last year, adding that “it would be important to evaluate in relation to HIV.”
Oxford agreed, and the Bill and Melinda Gates Foundation contributed $ 7.3 million, cementing its role as the linchpin of efforts to steer vaccine trials to the global south.
Even so, the process faced difficulties that larger studies with better resources in the US and Europe did not have. On the one hand, Dr. Madhi eliminate several test sites because they did not have sufficiently cold freezers or emergency power generators. This is necessary in a country where frequent power outages can put valuable doses at risk.
Even when the researchers locked down sites and relied on clinics with experience conducting HIV studies, the study was almost rolled back. The test results showed that almost half of the earliest volunteers were already infected with the virus at the time of vaccination, invalidating their results.
March 13, 2021, 6:38 p.m. ET
“We had a limited amount of funding and a limited number of vaccines,” said Dr. Cutland. “We were very concerned that the process had completely derailed.”
At another test location, all three pharmacists have signed Covid-19, incapacitating the only people who are allowed to prepare shots. Nurses in the study lost siblings and parents to the disease. The staff was so overwhelmed that the phones sometimes rang when vaccine managers called from abroad.
The magnitude of the pandemic in South Africa – 51,000 people have died and up to half the population may be infected – nearly overturned the process. But that was also part of what attracted vaccine makers: More cases mean faster results.
Dr. Madhi’s team weathered the storm, working 12-hour days, and adding last-minute swabs to make sure the volunteers weren’t already infected. By May he had asked Novavax, then a little-known American company with the support of the Trump administration, to conduct a lawsuit there too. Novavax agreed, and the Gates Foundation raised $ 15 million. However, the process was not registered until a few months later.
Novavax said the process took some time. However, the delay also reflected what scientists have called pressure on American-backed vaccine manufacturers to focus their efforts on the United States. Studies there are the best way to unlock coveted approvals from the Food and Drug Administration, the world’s gold standard drug agency.
And vaccine manufacturers usually know their largest markets best.
“Companies have the most extensive clinical trial experience in parts of the world that represent their commercial markets,” said Dr. Feinberg.
For vaccine manufacturers who have made supplying the world a core part of their strategies, the trials have been a boon. Novavax showed that the effectiveness of the vaccine was only moderately weakened by the variant in South Africa. Johnson & Johnson, who also conducted a South African study, showed that their vaccine was safe from hospitalization and death there.
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“You have your fishing line in the water – and by the time we were there the virus developed,” said Dr. Gregory Glenn, President of Research and Development at Novavax. “This is invaluable data for us and the world.”
In a recent laboratory study, the Oxford-AstraZeneca vaccine protected hamsters exposed to the variant from disease, even when the animals’ immune responses were slightly weaker. The human study in South Africa was too small to be able to say definitively whether the vaccine prevents serious diseases. Finding that it offers minimal protection from milder cases was itself disheartening as the shot remains the backbone of the introduction of many poorer countries.
In South Africa, the results failed because of plans to give the Oxford vaccine to health workers. Despite attempts, the country was unable to use them for early purchase contracts, which delayed delivery. Only a fifth of 1 percent of the people there have been vaccinated, raising fears of another wave of deaths and further mutations.
If HIV research laid the foundation for vaccine trials in South Africa, some scientists hope that an explosion in global studies on the pandemic will show drug companies that other countries also have the infrastructure to conduct larger studies.
To this end, the Gates-supported Coalition for Epidemic Preparedness Innovations offers companies incentives to conduct further Covid-19 vaccine trials in poorer countries.
“People tend to go for what they know,” said Melanie Saville, the coalition’s director of vaccine research and development. “However, capacity is increasing in low- and middle-income countries and we need to encourage developers to use it.”
Large numbers of South Africans volunteered for the trials. Most mornings, Dr. Anthonet Koen, who operated a location in Johannesburg for the Oxford and Novavax processes, opened their doors at 6 a.m. At this point, the participants had already been outside for two hours.
On December 11th, Dr. Koen that the pandemic was increasing: After weeks without a case, two people in the study tested positive. Then more and more every day. Health officials announced the discovery of the variant a week later. The random placement of the studies gave the scientists what they almost never had: an open-air laboratory where they could watch in real time how a vaccine and a variant stood in front of them.
Since the Oxford results were announced last month, volunteers have tried to comfort them: “I get a lot of condolences and ‘I’m sorry,'” she said.
As long as this vaccine prevents and other serious diseases, the world can live with the virus even in cases of the variant, scientists said. However, the trial in South Africa underscored the need to eradicate the virus before it mutates further. Without them, scientists said, the world could have been blind to what was to come.
“We would assume that these variants are not the end of the story,” said Andrew Pollard, the Oxford scientist responsible for his experiments. “For the virus to survive, it must continue to mutate once populations have good immunity to the current variants.”
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