LONDON —In the global race to counter the coronavirus pandemic, scientists in Britain, Germany, China and the United States are pushing to develop and possibly manufacture millions of doses of vaccine in a whole new way.
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This promising, but unproven, new generation of vaccine technologies relies on the deployment of a small piece of genetic code called messenger RNA to activate the immune system. It has never been approved for use before.
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But almost overnight, these cutting-edge RNA vaccine efforts have become prime candidates for fighting covid-19. Some developers plan to have tens of millions of doses ready by the end of the year.
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Elegant in theory, effective in the laboratory but not tested in the real world, potential RNA vaccines are especially attractive because they can be cheaper, easier, and faster to manufacture on a large scale: at least one team boasts that it could partner with developing country producers to provide millions of vials for as little as $ 5 per pop.
Multinational pharmaceutical companies, academic groups, and government laboratories around the world are developing more than 150 possible vaccines, many of which employ traditional protocols used to make flu vaccines and other vaccines for decades.
At least 17 teams are testing their possible vaccines in humans, and at least five of them are betting on RNA vaccines.
The RNA group has been among the first to come out because it can be rapidly designed on computers, using only the genetic sequence of the coronavirus that was shared online in early January.
Great risk, great rewards
The risks and the stakes are enormous.
“This is the largest scientific vaccination experiment ever done,” said Andrew Ward, a structural biologist at the Scripps Research Institute in San Diego. “He’s literally testing all the different technologies, and it’s going to be great to see how this all shakes up.”
The RNA vaccines under study come from a small laboratory at Imperial College London, from the People’s Liberation Army Academy of Military Sciences in China, from three major pharmaceutical companies: Pfizer, Moderna and CureVac, and their partners.
They are competing alongside groups pursuing a host of other methods, including using inactivated or dead viruses or virus fragments, a traditional strategy used against seasonal flu and other pathogens. Others use harmless viruses to transport distinctive pieces of the coronavirus machinery to cells.
Although never deployed to humans outside of clinical trials, RNA research is backed by hundreds of millions of dollars in investment, fueled by the urgency to crack the greedy code. Each team seeks the prize of being the first to receive a vaccine, while ensuring that their own populations will have early access.
It is a risky and high-priced gamble in 21st century computer-aided medicine.
Among the first to begin human trials is a self-powered RNA vaccine developed by British professor Robin Shattock, 57, who in his college days at North East Surrey College of Technology was not very good at math or science and thought maybe he would like me to be a rock star instead.
Ongoing human trials
Within days of the emergence of the new coronavirus in Wuhan, China, and its published genetic sequence, Shattock and his small team at Imperial College London went to work.
In January, February and March, Shattock was unable to answer his phone calls from senior British officials. He spent days of precious lab time soliciting and cajoling funds to advance his vaccine candidate, his allies said.
Then Britain’s Health Secretary Matt Hancock decided to endorse Shattock and his possible vaccine, and they contributed $ 50 million.
Last week, at an anonymous clinic in west London that cannot be named for security reasons, the first nine volunteers received a puncture from the Imperial College vaccine.
“They seem to have responded well,” said Shattock.
Another 300 volunteers will receive the dose during the summer. Imperial College hopes to launch a trial of 6,000 people in October.
“We believe that around the corner there will be a radical change in the way vaccines are developed and manufactured,” Shattock told The Washington Post. “I think we are on the cusp of that.”
If all goes well, a US trial of the first potential RNA vaccine will enter the crucial third phase to measure how well it protects against infection and disease this month. It is the gold standard for double-blind controlled studies involving thousands of volunteers in various countries. Half receive the candidate vaccine and the other half receive a placebo.
All potential vaccines share a common goal: to teach the immune system to recognize and neutralize the coronavirus. Newer approaches use genetic material such as RNA or DNA to turn body cells into miniature vaccine factories.
Shared genetic code
Some of the possible vaccines are breaking speed records.
Scientists were able to use the genetic sequence shared by researchers in China on January 10 to design possible vaccines on a computer before the coronavirus causing a mysterious pneumonia even had a name.
It took just two weeks for researchers at Imperial College to identify the piece of genetic material they wanted to deploy to try to trigger an immune response.
The main US effort, an RNA vaccine developed by the modern Massachusetts biotech company, went from a genetic sequence on a computer screen to an injection in a person’s arm in an unprecedented 66 days.
Leaders of Inovio Pharmaceuticals, a Pennsylvania company working on a possible DNA-using vaccine, have said it took three hours to design it.
The idea of deploying RNA to fight infectious diseases and cancer has tempted scientists for years. But they still have to go beyond the experimental stage.
Each vaccine technology has both advantages and disadvantages: the speed and flexibility of the RNA platform are balanced by a lack of experience in using it in large human populations.
Vaccines that may take longer to produce may offer a stronger immune response.
The utility of some vaccines may be limited in the developing world if they require extensive refrigeration. Questions remain about how long any of the potential vaccines could be effective and whether people might need booster shots.
Not ‘single silver bullet’
“No one thinks there will be a single silver bullet,” said Deborah Fuller, a microbiologist at the University of Washington.
This is because multiple treatments may be needed to meet the number of doses required worldwide, and vaccines are likely to have different profiles.
The faster it develops may not be the most effective. One might work better in older people than younger people, or vice versa.
“As a collective team, they will be able to combat this pandemic together,” Fuller said.
The RNA technology being tested in human volunteers is promising, but questions remain about safety, whether it works, and how long it can last.
“I don’t think we know,” said Peter Jay Hotez, dean of the Baylor College of Medicine’s National School of Tropical Medicine. “It’s a whole new technology, and we haven’t really had a large number of [vaccinated] people walking for years. ”
Pharmaceutical giant Pfizer and German firm BioNTech are testing four candidates for RNA vaccines in a clinical trial and reported the results of one of them this month. It uses a modified strand of RNA that encodes the spike protein found on the surface of the coronavirus, with an adjustment in its genetic code to increase its ability to trigger an immune response.
Such modifications “attempt to strike the right balance between stimulating the innate immune response, but not stimulating it so much that it shuts down the ability of RNA” to create the spike protein, said William Gruber, senior vice president, Pfizer Vaccine Clinical Research.
Cell Vaccine ‘Factory’
The Pfizer results, shared in a preprinted article that has not been peer-reviewed, showed that an RNA-based formula was safe at low doses and triggered a stronger immune reaction in people who were vaccinated than in those who recovered from a natural infection. Pfizer plans to test at least one of its possible RNA vaccines in a clinical trial of 30,000 people by the end of July, pending regulatory approval.
The expected RNA vaccines that are being tested by some of the groups mean that a smaller dose could be extremely potent, which could mean that people may need only a single dose.
The technology could also decrease the amount of genetic material needed in the future vaccine, making manufacturing more efficient.
Shattock said that a liter of his RNA reaction, worth about four cups, can produce at least 2 million doses of possible vaccine. Other vaccine models require thousands of liters to produce the same number of doses.
One of Pfizer’s candidates is a self-amplifying RNA vaccine.
“Once injected into a human being, a cell absorbs it and it’s like its own factory: it amplifies into the cell,” said Kathrin Jansen, director of vaccine research and development at Pfizer in May. Human trials began. “One copy comes in, and the factory starts coming in and making more and more copies.”
If the self-powered RNA vaccine is successful, Jansen said, it could allow the company to use a much smaller dose, and radically change the company’s predictions about how much vaccine it could make next year.
Pfizer has not chosen which of its four vaccines to increase, but has said it will make 1.2 billion doses next year.
Johnson reported from Boulder, Colorado.
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