Oct 3 (Insider) – This pandemic probably won’t be the last.
Experts warned in March of a “serious threat” from coronaviruses in the same family as SARS-CoV-2, the virus that caused the COVID-19 pandemic.
Ralph Baric, an epidemiologist at the University of North Carolina School of Medicine, told the New Scientist in March that it was “very easy to imagine” a new coronavirus emerging that was nearly as infectious as SARS-CoV-2 but far deadlier.
As of Friday, Johns Hopkins University had recorded roughly 234 million COVID-19 infections and 4.8 million deaths, for a death rate of about 2%. The virus’ true lethality is widely thought to be lower than that, since mild cases are more likely to go unrecorded than deaths. Either way, other coronaviruses that have emerged in recent years, though less infectious than the latest one, have been far deadlier.
The virus that causes MERS has killed about a third of people known to have caught it, while the SARS virus, which is technically known as SARS-CoV-1, has killed about 10% of people known to be infected.
In light of this, Dr. Anthony Fauci, President Joe Biden’s chief medical advisor, said at a public event in February that it would be “shame on us” if we don’t develop a “universal coronavirus vaccine.”
Scientists are trying to do just that.
Baric was one of the first scientists to study antibodies from people with COVID-19 to search for protection against other coronaviruses. His hope is to develop an all-in-one coronavirus vaccine that protects against numerous members of the SARS-CoV family.
He’s not alone. John Lewis, the CEO at the Canadian biotech company Entos, told Insider the company hoped to develop a single vaccine that protects against all coronaviruses by the end of the year.
But Entos, and more than 20 other groups worldwide racing to develop all-in-one vaccines, face a difficult road ahead. Entos acknowledged that it needed a partnership with a pharmaceutical company to both fund and make the vaccine. It also needs to convince regulators of its approach, which is far from guaranteed.
The science of targeting numerous coronaviruses at once is already difficult — and turning that research into a working vaccine will involve experimentation in expensive human trials. Dr. Dennis Burton, the chair at the Department of Immunology and Microbiology at Scripps Research, said getting vaccines into humans was a “bit of a black box.”
“We can make certain predictions, but how people respond to vaccines is complex,” he told Insider. “We’re all very different and it’s got to work globally.”
Even if a broad coronavirus vaccine works, it may not be able to prevent local virus outbreaks, Burton said. “But at least if you have something that can respond quickly and contain it within an area before it gets out of control and becomes a pandemic,” he added.
How vaccines can target numerous coronaviruses
The coronavirus family shares similar features. The goal of so-called broadly protective coronavirus vaccines is to get the body to react to parts of the viruses that are common to the whole family. These are called conserved sites. They are usually fundamental to the virus’ functioning and therefore are less likely to mutate.
In theory, if you’re vaccinated with a broadly protective shot, your body will fight any future coronaviruses that have yet to cross from animals to humans, so long as they have the common conserved site. These vaccines promise better protection than “variant-proof” vaccines, also in development, which are specifically meant to fight multiple SARS-CoV-2 variants in one go.
Emerging evidence suggests antibodies for one coronavirus protect against another, suggesting all-in-one coronavirus booster shots could work.
A study published in the New England Journal of Medicine on August 18 from Duke-NUS Medical School in Singapore found that people who caught SARS in 2003 and then later got Pfizer-BioNTech’s COVID-19 vaccine produced antibodies that protected against all known variants that cause COVID-19, as well as other coronaviruses carried by animals.
Wang Linfa, the study’s author, said in a statement at the time that the findings could help development of “next-generation vaccines” that “not only help us control the current COVID-19 pandemic, but may also prevent or reduce the risk of future pandemics caused by related viruses.”
Dr. Eric Topol, the director of the Scripps Research Translational Institute, said on Twitter when the study was published that “we keep getting closer to discovering antibodies” that protect across the “beta” subtype of coronaviruses, which includes the SARS virus, the MERS virus, and SARS-CoV-2.
“I don’t understand why we are futzing around with variant-specific vaccines, when this could be our number one priority,” he said.
The broadest possible immune response
To fend off more than one coronavirus, the conserved site must trigger the body’s immune response. This gives vaccine developers two routes for protection.
First, the antibody response, which blocks a virus from entering cells, and, second, the T-cell response, which identifies and destroys any cells that get infected. The location of a conserved sites usually dictates the type of immune response.
We don’t yet know which approach is best for all-in-one coronavirus vaccines, but companies such as Entos and the US immunotherapy firm Gritstone are using machine learning to search for virus sites that trigger T-cell responses.
Entos’ Lewis said one conserved site was 95% similar across all SARS-CoV-2 variants driving the ongoing pandemic. If a vaccine generated a strong T-cell response against this part of the virus, he said, “you would effectively gain control over all the currently circulating variants and then potentially more broadly against other coronaviruses.”
Lewis added that it would be “a big hurdle” to convince regulators of T-cell-inducing vaccines. His reasoning is that the antibody response would probably be much lower than for the COVID-19 vaccines from Pfizer-BioNTech and Moderna — and regulators have focused on antibody levels in the past.
But he remains optimistic. “If we get a pharmaceutical partnership and convince the regulator of our approach, we could get a broadly protective coronavirus vaccine done by the end of the year,” he said.
Gritstone is trying to find both conserved sites that trigger antibodies and fragments of the virus that can be recognized by T-cells. “The virus has a finite number of ways of escaping from our immune systems,” Andrew Allen, Gritstone’s CEO, told Insider, “and the more avenues we can block off, the better.”
Allen said that Gritstone planned to develop a vaccine that protected against multiple coronaviruses but that a true pan-coronavirus vaccine might be out of reach because of the variations among viruses in the family.
This is because coronaviruses, despite similarities, can vary a lot from one another.
Karin Jooss, the chief scientific officer at Gritstone, told Insider that the MERS and SARS viruses differed by about 60%, and the company hadn’t yet found a common region that it could target with a vaccine.
Antibodies are ‘critical’
Burton said T cells were probably important to tackling coronaviruses, but he described antibodies as “critical.”
Scientists at the Duke Human Vaccine Institute are focused on a vaccine that generates antibodies against the beta coronavirus subgroup.
They have discovered that parts of the viruses that attach to human cells are preserved across beta coronaviruses. These common sites trigger an antibody response.
A lab study from May found the Duke vaccine technology blocked numerous coronaviruses from entering cells.
This type of research is promising, but, as John Moore, a professor of microbiology and immunology at Weill Cornell Medical College, told Insider, it’s “early-stage.”
The biggest hurdle will be getting it out of the lab and into humans, which involves costly trials and expensive materials, he said.
Kevin Saunders, an assistant professor at the Department of Immunology at Duke, who leads the Duke team, said he needed $20 million to get the project out of the lab and into an early-stage human study of 50 people.
It’s a high hurdle, no doubt — but similarly lofty would be the rewards for getting it right. “We hope,” Entos’ Lewis said, “it will be the last booster you’ll need.”