Merck locates frozen batch of undisclosed Ebola vaccine, will donate for testing in Uganda’s outbreak | Science
In a revelation that may help Uganda combat its outbreak of Ebola, the pharmaceutical giant Merck has acknowledged to Science—after repeated inquiries—that it has up to 100,000 doses of an experimental vaccine for the deadly viral disease in its freezers in Pennsylvania and will donate them. The World Health Organization (WHO) and the Ugandan government are discussing if and how these doses can be incorporated into one or more clinical trials of other candidate Ebola vaccines that could launch as soon as next month.
The Merck vaccine targets Sudan ebolavirus, the pathogen currently circulating in Uganda. Merck quietly made the product in 2015 and 2016, soon after it had a landmark success with a similar vaccine against Zaire ebolavirus, a different virus that caused a big epidemic in West Africa between 2014 and 2016. The company froze the Sudan Ebola vaccine in bulk form and never tested it on people. But it has been shown to protect monkeys challenged with Sudan ebolavirus, and given the efficacy of Merck’s Zaire Ebola vaccine, scientists have high hopes that the Sudan Ebola shots will be safe and effective as well.
Merck’s disclosure “is amazingly good news,” says Mark Feinberg, who led the company’s program to develop the Zaire Ebola vaccine. “It allows this very promising vaccine to move forward quicker than would have otherwise been possible.” Feinberg left Merck in 2015 and now heads the vaccine non-profit IAVI, which is developing its own vaccine for Sudan ebolavirus. He tells Science he had no idea his old employer had made its own candidate vaccine against the virus.
Merck’s vaccine has not previously come up in public discussions of how to tackle the new Uganda outbreak and the company has issued confusing messages to Science about it in recent weeks. In an email sent on 13 October, Merck acknowledged for the first time it had made the vaccine but said vials of it had expired and were destroyed in 2021. After further questions, the company replied that the vaccine still existed in bulk, testing had confirmed those dose were viable, and they would be donated.
Merck says it plans to now perform a “fill and finish,” a process that puts bulk product into vials, and expects that to take about a month. The company will pay for it. “We’re doing everything to move it as quickly as we possibly can,” says Beth-Ann Coller, a virologist at the company who has headed product development for the company’s Ebola vaccines since May 2015.
According to a Ugandan Ministry of Health update on 22 October, Sudan ebolavirus has sickened 75 people in Uganda, killing 28 of them. The outbreak, Uganda’s first since 2012, is especially threatening because a few cases have occurred in Kampala, a bustling city of 1.5 million. The Ugandan government has placed two affected districts under lockdown.
Classic public health measures such as isolating patients and quarantining their contacts can bring Ebola outbreaks to an end, but it’s often difficult. Merck’s unexpected announcement has buoyed hopes that Uganda can stop the outbreak more quickly. “The potential availability of large volumes of vaccine that can be tested sooner is potentially game changing,” says Nicole Lurie, the U.S. director for the Coalition for Epidemic Preparedness Innovations (CEPI), a nonprofit that funds vaccine development to prevent pandemics.
Merck’s vaccine consists of the gene for the surface protein of the Sudan ebolavirus stitched into vesicular stomatitis virus (VSV), a livestock pathogen that rarely causes harm in humans. A similar vaccine against Zaire ebolavirus proved highly effective during a 2015 trial in Guinea, one of three countries ravaged by the West African epidemic, the largest ever recorded. That vaccine has since received approval from regulators in the United States and the European Union.
Two other developers of Sudan Ebola vaccines, the nonprofit Sabin Institute and the University of Oxford, both use chimpanzee adenoviruses to ferry the surface protein gene into the human body. Both are racing to produce enough doses to enter trials in Uganda. Sabin has 40,000 bulk doses and is working with CEPI to find a company that can do the fill and finish. Oxford has teamed up with the Serum Institute of India.
“Now there’s this other wildcard,” Lurie says.
Several scientists tell Science they are confident all three Sudan Ebola vaccines will protect people to varying degrees but they consider Merck’s vaccine the most promising candidate, because VSV—unlike the chimp adenoviruses—copies itself, leading to rapid to immunity. The VSV vaccines have also shown more robust and durable protection in monkey studies, and the Ebola Zaire version, marketed as Ervebo, has recently helped stem several outbreaks.
WHO was already collaborating with health officials in Uganda to design a protocol to test the Oxford and Sabin candidates with a strategy known as a “ring vaccination,” in which shots are offered to direct contacts of infected people (and possibly contacts of contacts). That approach was also used in the Guinea trial of the Zaire version. An independent “expert group is currently reviewing the evidence and will advise on which vaccine(s) to test first,” a WHO spokesperson wrote to Science.
Small market
Ebola vaccines have a long, tortured history. The VSV platform used in Merck’s shots was first developed nearly 20 years ago by virologists Heinz Feldmann, then with the Public Health Agency of Canada (PHAC), and Thomas Geisbert, then with the U.S. Army Medical Research Institute of Infectious Diseases. They showed that a single dose of a vaccine protected 100% of monkeys against an otherwise lethal dose of Zaire ebolavirus given 28 days later. Smaller animal studies showed a vaccine against the Sudan ebolavirus based on the VSV platform had promise as well. (In 2016, Science published a survey of 50 leading vaccine researchers who ranked the Sudan ebolavirus vaccine as the number one R&D priority based on feasibility and need.)
But pharmaceutical companies took little interest in Ebola vaccines because the market is so small. For decades, outbreaks involved a few hundred cases at most, usually in rural areas in Africa where the virus spread slowly, so there was little incentive to invest in the shots. In 2010, PHAC licensed the vaccines to NewLink Genetics, a small biotech that did nothing with it.
Then came West Africa’s Zaire outbreak, which engulfed the capitals of Guinea, Sierra Leone, and Liberia in 2014 and sickened tens of thousands of people in a matter of months, including a handful in Mali, Senegal, Nigeria, the United States, Europe. Geisbert and Feldmann were deeply dispirited because their vaccine had languished. “It was really frustrating because we had vaccines that were developed back in the early 2000s, and we knew that they would work, but we’re just lab guys,” says Geisbert, who now has a lab at the University of Texas Medical Branch.
In late September 2014, scientists at the U.S. Centers for Disease Control and Prevention projected that if control measures didn’t improve, Sierra Leone and Liberia together could have between 550,000 and 1.4 million Ebola cases by January 2015. That’s when Merck decided to license the vaccine from NewLink Genetics, Feinberg says. “Merck knew from the very beginning, that it was not going to be a profitable product,” he says. “They were moving it specifically for the public health reasons.”
Other major vaccine makers jumped in to develop their own candidates, but by then public health measures and behavior changes began to put the brakes on West Africa’s epidemic, causing cases to fall. (All told, nearly 29,000 people fell ill and more than 11,000 died.) Merck’s ring vaccination trial in Guinea, conducted with WHO and local health officials, crossed the finish line in mid-2015, just before the epidemic ended, but other candidates were too late. GSK later decided to give away its vaccine to the Sabin Institute.
Merck’s Ervebo is now a standard part of the response during outbreaks of Zaire ebolavirus. More than 300,000 people were vaccinated during the world’s second largest Ebola outbreak, for example, which caused 3470 reported cases in a conflict-riven area of the Democratic Republic of the Congo between 2018 and 2020.
But Merck has no interest in developing the vaccine for Sudan ebolavirus. In 2017, it gave the license for that vaccine back to PHAC, which subsequently cut a licensing deal with IAVI. In 2021, the U.S. government’s Biomedical Advanced Research and Development Authority (BARDA) awarded IAVI a grant worth up to $126 million to use upgraded technology to develop VSV-based vaccines for both Sudan ebolavirus and the related filovirus that causes Marburg disease, another rare but often lethal infection. (BARDA awarded a similar amount to Sabin to develop the same vaccines using its chimp adenovirus platform.)
Those vaccines are still at early stages of development, and when the Uganda outbreak began in September 2022, Geisbert was once again beside himself. “I sent an email to my boss and said, Look, we are in the same situation as in 2014,” he says. “The VSV vaccine we know works in ring vaccination, and it would be perfect to stop this.” Geisbert also now has unpublished data showing that the VSV Sudan ebolavirus vaccine provides robust protection in the monkey model.
Conflicting emails
Now, it has become clear that a big batch of Merck’s Sudan Ebola vaccine is available and could soon be ready for clinical trials.
After Feinberg left Merck in 2015, virologist Richard Peluso, who then ran vaccine bioprocessing for the company, says he told his boss, senior vice president of R&D Joe Miletich, that if the Zaire Ebola vaccine was safe and effective, the company had “an obligation to the world” to use the VSV platform to also make a stock of Sudan Ebola vaccine. Merck proceeded to make the vaccine under strict “good manufacturing practices” and also produced a large batch of a VSV-based Marburg vaccine.
When and how the company came to realize those stocks still exist today is not entirely clear. Science asked Merck on 13 October whether the company had produced the Sudan Ebola vaccine and retained stocks of it. A spokesperson emailed back that Merck had made approximately 70,000 vials of it in 2015-16. “The vials of Sudan ebolavirus (SUDV) vaccine candidate expired in 2021 and were destroyed,” the email added. (The email also said Merck had destroyed 96,000 filled vials of its Marburg vaccine.)
In response to follow-up questions, Merck acknowledged on 20 October that the company did retain bulk quantities of the frozen Ebola vaccine and arranged an interview with Coller. She says Merck destroyed the fill-and-finished doses of the Sudan Ebola vaccine because the vials had used rubber stoppers. “The stoppers become brittle when they’re stored frozen,” she explains.
The bulk product Merck has now disclosed had reached “the end of its shelf life,” she adds. The vaccine was destined for destruction as well, but to the surprise of company scientists, it still was in the freezer. “Frankly, fortuitously, it hadn’t yet been destroyed,” she says. “We immediately looked at that and said, Oh, my goodness, we can perhaps do something to help.” (Bulk Marburg vaccine, Coller says, was destroyed.)
Coller says she initiated a search to see if any Sudan Ebola vaccine remained after attending a WHO meeting that ended on 6 October in which she learned Uganda’s outbreak was rapidly growing. Asked why the company did not mention the find in response to Science’s 13 October email, she says Merck was still conducting tests to assess whether the vaccine had remained free of contaminants. “We were not sure about whether or not we would be able to use that bulk material and didn’t want to speak out of turn until we knew that there was something that we could actually do with it,” Coller says.
Merck never ran human studies with the Sudan Ebola vaccine. “That was not something that was ever really put on the table,” said Coller, noting that there has not been an outbreak of this virus anywhere since Uganda’s last one in 2012. “With hindsight, perhaps it could have been done better.”
In a revelation that may help Uganda combat its outbreak of Ebola, the pharmaceutical giant Merck has acknowledged to Science—after repeated inquiries—that it has up to 100,000 doses of an experimental vaccine for the deadly viral disease in its freezers in Pennsylvania and will donate them. The World Health Organization (WHO) and the Ugandan government are discussing if and how these doses can be incorporated into one or more clinical trials of other candidate Ebola vaccines that could launch as soon as next month.
The Merck vaccine targets Sudan ebolavirus, the pathogen currently circulating in Uganda. Merck quietly made the product in 2015 and 2016, soon after it had a landmark success with a similar vaccine against Zaire ebolavirus, a different virus that caused a big epidemic in West Africa between 2014 and 2016. The company froze the Sudan Ebola vaccine in bulk form and never tested it on people. But it has been shown to protect monkeys challenged with Sudan ebolavirus, and given the efficacy of Merck’s Zaire Ebola vaccine, scientists have high hopes that the Sudan Ebola shots will be safe and effective as well.
Merck’s disclosure “is amazingly good news,” says Mark Feinberg, who led the company’s program to develop the Zaire Ebola vaccine. “It allows this very promising vaccine to move forward quicker than would have otherwise been possible.” Feinberg left Merck in 2015 and now heads the vaccine non-profit IAVI, which is developing its own vaccine for Sudan ebolavirus. He tells Science he had no idea his old employer had made its own candidate vaccine against the virus.
Merck’s vaccine has not previously come up in public discussions of how to tackle the new Uganda outbreak and the company has issued confusing messages to Science about it in recent weeks. In an email sent on 13 October, Merck acknowledged for the first time it had made the vaccine but said vials of it had expired and were destroyed in 2021. After further questions, the company replied that the vaccine still existed in bulk, testing had confirmed those dose were viable, and they would be donated.
Merck says it plans to now perform a “fill and finish,” a process that puts bulk product into vials, and expects that to take about a month. The company will pay for it. “We’re doing everything to move it as quickly as we possibly can,” says Beth-Ann Coller, a virologist at the company who has headed product development for the company’s Ebola vaccines since May 2015.
According to a Ugandan Ministry of Health update on 22 October, Sudan ebolavirus has sickened 75 people in Uganda, killing 28 of them. The outbreak, Uganda’s first since 2012, is especially threatening because a few cases have occurred in Kampala, a bustling city of 1.5 million. The Ugandan government has placed two affected districts under lockdown.
Classic public health measures such as isolating patients and quarantining their contacts can bring Ebola outbreaks to an end, but it’s often difficult. Merck’s unexpected announcement has buoyed hopes that Uganda can stop the outbreak more quickly. “The potential availability of large volumes of vaccine that can be tested sooner is potentially game changing,” says Nicole Lurie, the U.S. director for the Coalition for Epidemic Preparedness Innovations (CEPI), a nonprofit that funds vaccine development to prevent pandemics.
Merck’s vaccine consists of the gene for the surface protein of the Sudan ebolavirus stitched into vesicular stomatitis virus (VSV), a livestock pathogen that rarely causes harm in humans. A similar vaccine against Zaire ebolavirus proved highly effective during a 2015 trial in Guinea, one of three countries ravaged by the West African epidemic, the largest ever recorded. That vaccine has since received approval from regulators in the United States and the European Union.
Two other developers of Sudan Ebola vaccines, the nonprofit Sabin Institute and the University of Oxford, both use chimpanzee adenoviruses to ferry the surface protein gene into the human body. Both are racing to produce enough doses to enter trials in Uganda. Sabin has 40,000 bulk doses and is working with CEPI to find a company that can do the fill and finish. Oxford has teamed up with the Serum Institute of India.
“Now there’s this other wildcard,” Lurie says.
Several scientists tell Science they are confident all three Sudan Ebola vaccines will protect people to varying degrees but they consider Merck’s vaccine the most promising candidate, because VSV—unlike the chimp adenoviruses—copies itself, leading to rapid to immunity. The VSV vaccines have also shown more robust and durable protection in monkey studies, and the Ebola Zaire version, marketed as Ervebo, has recently helped stem several outbreaks.
WHO was already collaborating with health officials in Uganda to design a protocol to test the Oxford and Sabin candidates with a strategy known as a “ring vaccination,” in which shots are offered to direct contacts of infected people (and possibly contacts of contacts). That approach was also used in the Guinea trial of the Zaire version. An independent “expert group is currently reviewing the evidence and will advise on which vaccine(s) to test first,” a WHO spokesperson wrote to Science.
Small market
Ebola vaccines have a long, tortured history. The VSV platform used in Merck’s shots was first developed nearly 20 years ago by virologists Heinz Feldmann, then with the Public Health Agency of Canada (PHAC), and Thomas Geisbert, then with the U.S. Army Medical Research Institute of Infectious Diseases. They showed that a single dose of a vaccine protected 100% of monkeys against an otherwise lethal dose of Zaire ebolavirus given 28 days later. Smaller animal studies showed a vaccine against the Sudan ebolavirus based on the VSV platform had promise as well. (In 2016, Science published a survey of 50 leading vaccine researchers who ranked the Sudan ebolavirus vaccine as the number one R&D priority based on feasibility and need.)
But pharmaceutical companies took little interest in Ebola vaccines because the market is so small. For decades, outbreaks involved a few hundred cases at most, usually in rural areas in Africa where the virus spread slowly, so there was little incentive to invest in the shots. In 2010, PHAC licensed the vaccines to NewLink Genetics, a small biotech that did nothing with it.
Then came West Africa’s Zaire outbreak, which engulfed the capitals of Guinea, Sierra Leone, and Liberia in 2014 and sickened tens of thousands of people in a matter of months, including a handful in Mali, Senegal, Nigeria, the United States, Europe. Geisbert and Feldmann were deeply dispirited because their vaccine had languished. “It was really frustrating because we had vaccines that were developed back in the early 2000s, and we knew that they would work, but we’re just lab guys,” says Geisbert, who now has a lab at the University of Texas Medical Branch.
In late September 2014, scientists at the U.S. Centers for Disease Control and Prevention projected that if control measures didn’t improve, Sierra Leone and Liberia together could have between 550,000 and 1.4 million Ebola cases by January 2015. That’s when Merck decided to license the vaccine from NewLink Genetics, Feinberg says. “Merck knew from the very beginning, that it was not going to be a profitable product,” he says. “They were moving it specifically for the public health reasons.”
Other major vaccine makers jumped in to develop their own candidates, but by then public health measures and behavior changes began to put the brakes on West Africa’s epidemic, causing cases to fall. (All told, nearly 29,000 people fell ill and more than 11,000 died.) Merck’s ring vaccination trial in Guinea, conducted with WHO and local health officials, crossed the finish line in mid-2015, just before the epidemic ended, but other candidates were too late. GSK later decided to give away its vaccine to the Sabin Institute.
Merck’s Ervebo is now a standard part of the response during outbreaks of Zaire ebolavirus. More than 300,000 people were vaccinated during the world’s second largest Ebola outbreak, for example, which caused 3470 reported cases in a conflict-riven area of the Democratic Republic of the Congo between 2018 and 2020.
But Merck has no interest in developing the vaccine for Sudan ebolavirus. In 2017, it gave the license for that vaccine back to PHAC, which subsequently cut a licensing deal with IAVI. In 2021, the U.S. government’s Biomedical Advanced Research and Development Authority (BARDA) awarded IAVI a grant worth up to $126 million to use upgraded technology to develop VSV-based vaccines for both Sudan ebolavirus and the related filovirus that causes Marburg disease, another rare but often lethal infection. (BARDA awarded a similar amount to Sabin to develop the same vaccines using its chimp adenovirus platform.)
Those vaccines are still at early stages of development, and when the Uganda outbreak began in September 2022, Geisbert was once again beside himself. “I sent an email to my boss and said, Look, we are in the same situation as in 2014,” he says. “The VSV vaccine we know works in ring vaccination, and it would be perfect to stop this.” Geisbert also now has unpublished data showing that the VSV Sudan ebolavirus vaccine provides robust protection in the monkey model.
Conflicting emails
Now, it has become clear that a big batch of Merck’s Sudan Ebola vaccine is available and could soon be ready for clinical trials.
After Feinberg left Merck in 2015, virologist Richard Peluso, who then ran vaccine bioprocessing for the company, says he told his boss, senior vice president of R&D Joe Miletich, that if the Zaire Ebola vaccine was safe and effective, the company had “an obligation to the world” to use the VSV platform to also make a stock of Sudan Ebola vaccine. Merck proceeded to make the vaccine under strict “good manufacturing practices” and also produced a large batch of a VSV-based Marburg vaccine.
When and how the company came to realize those stocks still exist today is not entirely clear. Science asked Merck on 13 October whether the company had produced the Sudan Ebola vaccine and retained stocks of it. A spokesperson emailed back that Merck had made approximately 70,000 vials of it in 2015-16. “The vials of Sudan ebolavirus (SUDV) vaccine candidate expired in 2021 and were destroyed,” the email added. (The email also said Merck had destroyed 96,000 filled vials of its Marburg vaccine.)
In response to follow-up questions, Merck acknowledged on 20 October that the company did retain bulk quantities of the frozen Ebola vaccine and arranged an interview with Coller. She says Merck destroyed the fill-and-finished doses of the Sudan Ebola vaccine because the vials had used rubber stoppers. “The stoppers become brittle when they’re stored frozen,” she explains.
The bulk product Merck has now disclosed had reached “the end of its shelf life,” she adds. The vaccine was destined for destruction as well, but to the surprise of company scientists, it still was in the freezer. “Frankly, fortuitously, it hadn’t yet been destroyed,” she says. “We immediately looked at that and said, Oh, my goodness, we can perhaps do something to help.” (Bulk Marburg vaccine, Coller says, was destroyed.)
Coller says she initiated a search to see if any Sudan Ebola vaccine remained after attending a WHO meeting that ended on 6 October in which she learned Uganda’s outbreak was rapidly growing. Asked why the company did not mention the find in response to Science’s 13 October email, she says Merck was still conducting tests to assess whether the vaccine had remained free of contaminants. “We were not sure about whether or not we would be able to use that bulk material and didn’t want to speak out of turn until we knew that there was something that we could actually do with it,” Coller says.
Merck never ran human studies with the Sudan Ebola vaccine. “That was not something that was ever really put on the table,” said Coller, noting that there has not been an outbreak of this virus anywhere since Uganda’s last one in 2012. “With hindsight, perhaps it could have been done better.”
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