Could a single vaccine work against all coronaviruses?

The invention of the Covid-19 vaccines will be remembered as a milestone in the history of medicine, creating within months what took up to a decade before. But Dr. Kayvon Modjarrad, director of the Emerging Infectious Diseases branch at the Walter Reed Army Research Institute in Silver Springs, Md., Is not satisfied.

“It’s not fast enough,” he said. More than 2.3 million people worldwide have died and many countries will not have full access to vaccines for a year or two: “Fast – really fast – is having it there from day one . “

There will be more coronavirus outbreaks in the future. Bats and other mammals are teeming with strains and species of this abundant virus family. Some of these pathogens will inevitably overwhelm the species barrier and cause further pandemics. It’s just a matter of time.

Dr Modjarrad is one of many scientists who have been calling for a different type of vaccine for years: a vaccine that could work against all coronaviruses. These calls were largely ignored until Covid-19 demonstrates how disastrous coronaviruses can be.

Now researchers are starting to develop prototypes of a so-called pancoronavirus vaccine, with some showing promise, even so early on. results of animal experiments. Dr Eric Topol, professor of molecular medicine at the Scripps Research Institute in San Diego, believes scientists should immediately join another large-scale vaccine creation project.

“We have to have a real workforce to accelerate this, so that we can have it this year,” he said. Dr Topol and Dennis Burton, an immunologist at Scripps, called for the broad-spectrum coronavirus vaccine project on Monday in the journal Nature.

After coronaviruses were first identified in the 1960s, they did not become a priority for vaccine makers. For decades, it seemed like they only caused mild colds. But in 2002, a new coronavirus called SARS-CoV emerged, causing fatal pneumonia called severe acute respiratory syndrome, or SARS. Scientists rushed to make a vaccine for it.

Since no one had yet made a coronavirus vaccine for humans, there was a lot to learn about its biology. Ultimately, the researchers chose a target for immunity: a protein on the surface of the virus, called a peak. Antibodies that stick to the peak can prevent the coronavirus from entering cells and stop an infection.

However, public health officials in Asia and elsewhere did not wait for the invention of a SARS vaccine to get to work. Their quarantines and other efforts have proven to be remarkably effective. Within months, they wiped out SARS-CoV, with just 774 deaths along the way.

The danger of coronaviruses became even clearer in 2012, when a second species spread to bats, causing another deadly respiratory disease called MERS. Researchers have started working on MERS vaccines. But some researchers have questioned whether making a new vaccine for each new coronavirus – what Dr Modjarrad calls the “one bug, one drug approach” – was the smartest strategy. Wouldn’t it be better, they thought, if a single vaccine could work against SARS, MERS and any other coronavirus?

This idea sat nowhere for years. MERS and SARS caused relatively few deaths and were quickly eclipsed by outbreaks of other viruses such as Ebola and Zika.

In 2016, Maria Elena Bottazzi, a virologist at Baylor College of Medicine, and her colleagues requested US government support to develop a vaccine against the pancoronavirus, but did not receive it. “They said there was no interest in pancorona,” recalls Dr. Bottazzi.

His team even lost funding to develop a SARS vaccine after it was shown to work in mice, was not toxic to human cells, and could be manufactured on a large scale. A coronavirus that had vanished from sight was just not a top priority.

Without enough money to start clinical trials, scientists kept their SARS vaccine in a freezer and moved on to other research. “It’s been a struggle,” said Dr Bottazzi.

Dr Matthew Memoli, a virologist at the National Institute of Allergy and Infectious Diseases, sees these decisions as a huge mistake. “It’s a failure of our science system,” he said. “Funders tend to chase after shiny objects.”

Three years later, a third dangerous coronavirus appeared: the SARS-CoV-2 strain at the origin of Covid-19. Although this virus has a much lower death rate than its cousins ​​responsible for SARS and MERS, it spreads much better from person to person, resulting in more than 106 million documented cases in the world. world and continues to climb.

All the lessons researchers learned about coronaviruses helped them move quickly to make new SARS-CoV-2 vaccines. Dr Bottazzi and her colleagues used the technology they had created to make SARS vaccines to make one against Covid-19, which is currently in early clinical trials.

Other researchers have used even more recent methods to go faster. German company BioNTech created a genetic molecule called messenger RNA that encoded the spike protein. In partnership with Pfizer, the companies received US government clearance for their vaccine in just 11 months. The previous record for a chickenpox vaccine was four years.

Although the Covid-19 pandemic is still far from over, a number of researchers are calling for preparations for the next deadly coronavirus.

“This has happened three times already,” said Daniel Hoft, virologist at Saint Louis University. “It’s very likely going to happen again.”

Researchers at VBI Vaccines, a Cambridge-based company, took a small step towards a vaccine against the pancoronavirus last summer. They created virus-like shells sprinkled with advanced proteins from the three coronaviruses that caused SARS, MERS and Covid-19.

When the researchers injected the mice with this tri-tip vaccine, the animals made antibodies that worked against all three coronaviruses. Oddly enough, some of these antibodies could also latch onto a fourth human coronavirus that causes seasonal colds – even if that virus’s spike proteins were not included in the vaccine. Scientists have made this data public but have not yet published it in a scientific journal.

David Anderson, scientific director of VBI, said it was not clear why the vaccine worked this way. One possibility is that an immune cell presented with several versions of a protein at a time does not make antibodies against just one. Instead, it makes a compromise antibody that works against them all.

“You’re educating him,” Dr Anderson said, although he cautioned that this was speculation at the moment.

Last month, Pamela Bjorkman, structural biologist at Caltech, and her colleagues published a more in-depth experiment with a universal vaccine against the coronavirus in the journal Science. The researchers attached only the spike protein spikes of eight different coronaviruses to a protein core, known as a nanoparticle. After injecting these nanoparticles into mice, the animals generated antibodies that could stick to the eight coronaviruses – and four other coronaviruses that scientists had not used in the vaccine.

Dr Modjarrad is leading a team at Walter Reed developing another vaccine based on a nanoparticle dotted with fragments of proteins. They plan to start clinical trials on volunteers next month. Although the vaccine currently only uses protein fragments from peaks of SARS-CoV-2, Dr Modjarrad and his colleagues are preparing to revamp it as a vaccine against the pancoronavirus.

Dr Hoft of Saint Louis University is working on a universal vaccine that does not rely on antibodies to the spike protein. Together with Gritstone Oncology, a California-based biotechnology company, he created a vaccine that prompts cells to make surface proteins that can alert the immune system as if a coronavirus – any coronavirus – was present. They are currently preparing a clinical trial to see if it is effective against SARS-CoV-2.

“We are interested in developing maybe a third generation vaccine, which would be on the shelves and ready for the future epidemic,” said Dr Hoft.

Dr Topol thinks scientists should explore another strategy as well: finding antibodies against the pancoronavirus made by our own bodies during infections.

Researchers studying HIV and other viruses have found rare types among the billions of antibodies produced during infection that act against a wide variety of related strains. It might be possible to create vaccines that cause the body to produce copious amounts of these largely neutralizing antibodies.

Coronaviruses are quite similar to each other, said Dr Topol, that it might not be that difficult to create vaccines that produce neutralizing antibodies on a large scale. “They are a family of viruses that are easy to eliminate,” he said.

The search for a pancoronavirus vaccine 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 that will cross the cash barrier.

“I think we can have vaccines to prevent such pandemics,” Dr Memoli said. “None of us want to go through this again. And we don’t want our children to go through this again, or our grandchildren, or our descendants 100 years from now.