But some scientists believe a vaccine might already exist. Surprising new research in a niche area of immunology suggests that certain live vaccines that have been around for decades could, possibly, protect against the coronavirus. The theory is these vaccines could make people less likely to experience serious symptoms — or even any symptoms — if they catch it.
At more than 25 universities and clinical centers around the world, researchers have begun clinical trials, primarily in health care workers, to test whether a live tuberculosis vaccine that has been in use for 99 years called the bacillus Calmette-Guerin, or BCG, vaccine, could reduce the risks associated with the coronavirus. Another small but esteemed group of scientists is raising money to test the potential protective effects of a 60-year-old live polio vaccine called OPV.
It’s counter-intuitive to think that old vaccines created to fight very different pathogens could defend against the coronavirus. The idea is controversial in part because it challenges the dogma about how vaccines work.
But scientists’ understanding of an arm of immunology known as innate immunity has shifted in recent years. A growing body of research suggests that live vaccines, which are made from living but attenuated pathogens (as opposed to inactivated vaccines, which use dead pathogens) provide broad protection against infections in ways that no one anticipated.
“We can’t be certain as to what the outcome will be, but I suspect it’ll have an effect” on the coronavirus, said Jeffrey Cirillo, a microbiologist and immunologist at Texas A&M University who is leading one of the BCG trials. “Question is, how big will it be?” Scientists stress that these vaccines will not be a panacea. They might make symptoms milder, but they probably won’t eliminate them. And the protection, if it occurs, would most likely last only a few years.
Still, “these could be a first step,” said Dr Mihai Netea, an immunologist at Radboud University in the Netherlands who is leading another one of the trials. “They can be the bridge until you have the time to develop a specific vaccine.” The first evidence to suggest that live vaccines could be broadly protective trickled in nearly a century ago, but no one knew what to make of it. In 1927, soon after BCG was rolled out, Carl Naslund of the Swedish Tuberculosis Society observed that children vaccinated with the live tuberculosis vaccine were three times less likely to die of any cause compared with kids who weren’t.
“One is tempted to explain this very low mortality among vaccinated children by the idea that BCG vaccine provokes a non-specific immunity,” he wrote in 1932. Then, in clinical trials conducted in the 1940s and ’50s in the US and Britain, researchers found BCG reduced non-accidental deaths from causes other than tuberculosis by an average of 25 per cent. Also in the 1950s, Russian researchers, including Marina Voroshilova of the Academy of Medical Science in Moscow, noticed that people who had been given the live polio vaccine, compared with people who hadn’t, were far less likely to fall ill with the seasonal flu and other respiratory infections.
She and other scientists undertook a clinical trial involving 320,000 Russians to more carefully test these mysterious effects.
They found that among individuals who had received the live polio vaccine, “the incidence of seasonal influenza was reduced by 75 percent,” said Konstantin Chumakov, Voroshilova’s son, who is now an associate director for research in the US Food and Drug Administration’s Office of Vaccines Research and Review. Recent studies have produced similar findings. In a 2016 review of 68 papers commissioned by the World Health Organization, a team of researchers concluded that BCG, along with other live vaccines, “reduce overall mortality by more than would be expected through their effects on the diseases they prevent.”
The WHO has long been sceptical about these “non-specific effects,” in part because much of the research on them has involved observational studies that don’t establish cause and effect. But in a recent report incorporating newer results from some clinical trials, the organization described non-specific vaccine effects as “plausible and common.” Dr Stanley Plotkin, a vaccinologist and emeritus professor at the University of Pennsylvania who developed the rubella vaccine but has no involvement in the current research, agreed. “Vaccines can affect the immune system beyond the response to the specific pathogen,” he said.
Peter Aaby, a Danish anthropologist who has spent 40 years studying the non-specific effects of vaccines in Guinea-Bissau, in West Africa, and whose findings have been criticised as implausible, is hopeful that these trials will be a tipping point for research in the field. “It’s kind of a golden moment in terms of actually having this taken seriously,” he said. The possibility that vaccines could have non-specific effects is brow-furrowing in part because scientists have long believed that vaccines work by stimulating the body’s highly specific adaptive immune system.
After receiving a vaccine against, say, polio, a person’s body creates an army of poliospecific antibodies that recognise and attack the virus before it has a chance to take hold. Antibodies against polio can’t fight off infections caused by other pathogens, though — so, based on this framework, polio vaccines should not be able to reduce the risk associated with other viruses, such as the coronavirus.
But over the past decade, immunologists have discovered that live vaccines also stimulate the innate immune system, which is less specific but much faster. They have found that the innate immune system can be trained by live vaccines to better fight off various kinds of pathogens.
Such studies are “at the very bottom of the evidence hierarchy,” said Dr Christine Stabell Benn, who is raising funds for a Danish BCG trial. She added that the protective effects of a dose of BCG given to adults decades ago, when they were infants, may well differ from the protective effects the vaccine could provide when given to adults during an outbreak.
“In the end,” said Dr Netea, “only the clinical trials will give the answer.” Thankfully, that answer will come very soon. Initial results from the trials that are underway may be available within a few months. If these researchers are right, these old vaccines could buy us time — and save thousands of lives — while we work to develop a new one.
— Moyer is a science and health writer for NYT© 2020
The New York Times