The invention of Covid-19 vaccines will be remembered as a milestone in the history of medicine, leading to a decade within a few months. But dr. Kayvon Modjarrad, the director of the Emerging Diseases Branch at the Walter Reed Army Institute of Research in Silver Springs, MD, is not satisfied.
“It’s not fast enough,” he said. More than 2.3 million people around the world have died, and many countries have not had full access to the vaccines in a year or two: “Fast – really fast – get it on day one.”
There will be more coronavirus outbreaks in the future. Bats and other mammals are full of species and species family of viruses. Some of these pathogens will inevitably wash over the species boundary and cause new pandemics. It’s just a matter of time.
Dr. Modjarrad is one of the many scientists who have been asking for a different type of vaccine for years: one that can work against all coronaviruses. These calls were largely ignored until Covid-19 showed how disastrous coronaviruses can be.
Now researchers are beginning to develop prototypes of a so-called pancoronavirus vaccine, with some promising, if early, results of experiments on animals. Dr. Eric Topol, a professor of molecular medicine at the Scripps Research Institute in San Diego, believes scientists should immediately collaborate on another large-scale vaccine creation project.
“We need to get a real workforce to speed it up so we can have it this year,” he said. Dr. Topol and Dennis Burton, an immunologist at Scripps, asked in the journal Nature on Monday for this project on broad-spectrum coronavirus vaccines.
After coronaviruses were first identified in the 1960s, it did not become a high priority for vaccine manufacturers. For decades, it seemed to cause only mild colds. But in 2002, a new coronavirus called SARS-CoV emerged, causing a deadly pneumonia called severe acute respiratory syndrome, or SARS. Scientists have scrambled to make a vaccine for it.
Since no one had ever made a coronavirus vaccine for humans before, there was a lot to learn about its biology. Finally, researchers chose a target for immunity: a protein on the surface of the virus called spike. Antibodies that attach to the peak can prevent the coronavirus from entering cells and stopping an infection.
However, public health officials in Asia and elsewhere have not waited for a SARS vaccine to be invented. Their quarantines and other efforts were remarkably effective. Within months, they wiped out SARS-CoV, with only 774 deaths en route.
The danger of coronaviruses became even clearer in 2012 when a second species of bat spilled over, causing another deadly respiratory disease called MERS. Researchers have begun work on MERS vaccines. But some researchers have questioned whether the manufacture of a new vaccine for each new coronavirus – which dr. Modjarrad calls ‘the one mistake, one drug approach’ – the smartest strategy was. Wouldn’t it be better, they think, if a single vaccine could work against SARS, MERS and any other coronavirus?
That idea got nowhere for years. MERS and SARS caused relatively few deaths and were quickly obscured by outbreaks of other viruses such as Ebola and Zika.
In 2016, Maria Elena Bottazzi, a virologist at the Baylor College of Medicine, and her colleagues applied for support from the U.S. government to develop a vaccine against pancreatic virus, but did not receive it. “They said there is no interest in pancorona,” said Dr. Bottazzi remembers.
Her team even lost money for the development of a SARS vaccine after they showed that it works in mice, is not toxic to human cells and can be manufactured on a large scale. A coronavirus that disappeared from sight was simply not the highest priority.
Without enough money to start clinical trials, the scientists stored their SARS vaccine in a freezer and switched to other research. “It was a struggle,” Dr Bottazzi said.
Dr. Matthew Memoli, a virologist at the National Institute of Allergy and Infectious Diseases, considers these decisions to be a huge mistake. “This is a failure of our science system,” he said. “Funders tend to chase shiny objects.”
Three years later, a third dangerous coronavirus emerged: the SARS-CoV-2 strain that causes Covid-19. Although this virus has a much lower mortality rate than its cousins causing SARS and MERS, it works much better to spread from person to person, leading to more than 106 million documented cases worldwide and still climbing.
All the lessons researchers have learned about coronaviruses have helped them to get vaccinated quickly for SARS-CoV-2. Dr. Bottazzi and her colleagues used the technology they created to make SARS vaccines to make one for Covid-19, which is now in early clinical trials.
Other researchers have even used newer methods to move faster. The German company BioNTech has created a genetic molecule called messenger RNA that encodes the protein of the vein. In partnership with Pfizer, the companies obtained authorization from the US government for their vaccine in just 11 months. The previous record for a chickenpox vaccine was four years.
Although the Covid-19 pandemic is far from over, a number of researchers are asking for preparations for the next deadly coronavirus.
“It’s happened three times already,” said Daniel Hoft, a virologist at Saint Louis University. “It’s likely to happen again.”
Researchers from VBI vaccines, a company in Cambridge, took a small step towards a pancreatic virus vaccine last summer. They created virus-like shells, strewn with ear proteins from the three coronaviruses that caused SARS, MERS and Covid-19.
When the researchers injected this three-vein vaccine into mice, the animals made antibodies that worked against all three coronaviruses. Remarkably, some of the antibodies may also cling to a fourth human coronavirus causing seasonal colds, although the virus’ vein proteins have not been included in the vaccine. The scientists released this data but have not yet published it in a scientific journal.
David Anderson, head of science at VBI, said it was not clear why the vaccine worked that way. One possibility is that an immune cell with different versions of a protein does not simultaneously form antibodies against one. Instead, it’s a compromise that works against everyone.
“You learn it,” said Dr. Anderson said, though he warned it was speculation for now.
Last month, Pamela Bjorkman, a structural biologist at Caltech, and her colleagues published a more extensive experiment with a universal coronavirus vaccine in the journal Science. The researchers only attached the tips of vein proteins from eight different coronaviruses to a protein nucleus known as a nanoparticle. After the nanoparticles were injected into mice, the animals generated antibodies that could adhere to all eight coronaviruses – and against four other coronaviruses that the scientists did not use in the vaccine.
Dr Modjarrad leads a team led by Walter Reed to develop another vaccine based on a nanoparticle with protein fragments. They expect to begin clinical trials on volunteers next month. Although the vaccine currently uses only protein fragments of SARS-CoV-2 nails, dr. Modjarrad and his colleagues propose to reload it as a vaccine against pancreatic virus.
Dr. Hoft of Saint Louis University is working on a universal vaccine that is not dependent on antibodies against the protein of the vein. In collaboration with Gritstone Oncology, a California-based biotechnology company, he created a vaccine that asks cells to make proteins on the surface that can alert the immune system as if a coronavirus – any coronavirus – is present. They are now preparing a clinical trial to see if it is effective against SARS-CoV-2.
“We are interested in perhaps developing a third-generation vaccine that will be on the shelf and ready for the future outbreak,” said Dr. Hoft said.
Dr. Topol believes that scientists should also investigate another strategy: to look for antibodies to the pancoronavirus that are made by our own bodies during infections.
Researchers studying HIV and other viruses have, amidst the billions of antibodies that have emerged during an infection, discovered rare species that work against a wide variety of related strains. It may be possible to create vaccines that entice the body to make abundant amounts of these broad neutralizing antibodies.
Coronaviruses are similar to each other, said dr. Topol said that it may not be that difficult to build vaccines that neutralize antibodies in general. “It’s an easy family of viruses to take down,” he said.
The search for a vaccine against pancoronavirus may take longer than dr. Topol’s sunny expectations. But even if it takes a few years, it could help prepare the world for the next coronavirus to jump the species barrier.
“I think we can have vaccines to prevent pandemics like this,” said Dr. Memoli said. “None of us want to go through this again. And we do not want our children to go through this again, or our grandchildren or our descendants 100 years from now. ”