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While the world awaits a coronavirus vaccine, tens of thousands of people could die. But some scientists believe there could be a vaccine.
Surprising new research in a specific area of immunology suggests that certain live vaccines that have been around for decades could possibly protect against the coronavirus. The theory is that these vaccines could make people less likely to experience severe symptoms, or even any symptoms, if they detect it.
At more than 25 universities and clinical centers around the world, researchers have begun clinical trials, primarily on healthcare workers, to assess whether a live tuberculosis vaccine that has been in use for 99 years called the Calmette-Guérin bacillus, o BCG, vaccine, could reduce the risks associated with the coronavirus.
Another small but esteemed group of scientists is raising money to test the possible protective effects of a 60-year-old live polio vaccine called O.P.V.
It is counterintuitive to think that ancient vaccines created to combat very different pathogens could defend against the coronavirus. The idea is controversial in part because it challenges dogma about how vaccines work.
But scientists’ understanding of an immunology arm known as innate immunity has changed in recent years. A growing body of research suggests that live vaccines, which are made of live but attenuated pathogens (unlike inactivated vaccines, which use dead pathogens) provide extensive protection against infection in a way that no one had anticipated.
“We can’t be sure what the result will be, but I suspect it will have an effect” on the coronavirus, said Jeffrey Cirillo, a microbiologist and immunologist at Texas A&M University who leads one of the B.C.G. judgments. “The question is, how big will it be?”
Scientists emphasize that these vaccines will not be a panacea. They can make symptoms milder, but they probably won’t eliminate them. And the protection, if it occurs, would probably 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 trial. “They can be the bridge until I have time to develop a specific vaccine.”
The first evidence to suggest that live vaccines could be widely protective leaked almost a century ago, but no one knew what to do with them. In 1927, shortly after B.C.G. When it was launched, Carl Naslund of the Swedish Tuberculosis Society noted that children vaccinated with the live tuberculosis vaccine were three times less likely to die from any cause compared to children who were not.
“One is tempted to explain this very low mortality among vaccinated children by the idea that B.C.G. the vaccine causes nonspecific immunity,” he wrote in 1932.
Then, in clinical trials conducted in the 1940s and 1950s in the United States and Great Britain, the researchers discovered that B.C.G. It reduced non-accidental deaths from causes other than tuberculosis by an average of 25 percent.
Also in the 1950s, Russian researchers, including Marina Voroshilova of the Moscow Academy of Medical Sciences, noted that people who received the live polio vaccine, compared to people who did not, were much less likely of getting sick with the season. flu and other respiratory infections. She and other scientists conducted a clinical trial with 320,000 Russians to more carefully test these mysterious effects.
They found that among people who had received the live polio vaccine, “the incidence of seasonal influenza was reduced by 75 percent,” said Konstantin Chumakov, son of Voroshilova, who is now associate director of research at the Office of United States Food and Drug Administration. Vaccine research and review.
Recent studies have produced similar findings. In a 2016 review of 68 documents commissioned by the World Health Organization, a team of researchers concluded that BCG, along with other live vaccines, “reduces overall mortality by more than would be expected through its effects on diseases they prevent. ”
The OMS. You have long been skeptical of these “nonspecific effects,” in part because much of the research on them has involved observational studies that do not establish cause and effect. But in a recent report incorporating more recent results from some clinical trials, the organization described the nonspecific effects of the vaccine as “plausible and common.”
Dr. Stanley Plotkin, a vaccinologist and professor emeritus at the University of Pennsylvania who developed the rubella vaccine but is not involved 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 nonspecific effects of vaccines in Guinea-Bissau, in West Africa, and whose findings have been criticized as implausible, hopes that these trials will be a turning point for research in the countryside. . “It is a kind of golden moment in terms of this being taken seriously,” he said.
The possibility that vaccines may have nonspecific effects is partly narrow, partly because scientists have long believed that vaccines work by stimulating the body’s highly specific adaptive immune system.
After receiving a vaccine against, for example, polio, a person’s body creates an army of specific polio antibodies that recognize and attack the virus before they have a chance to get hold of it. However, polio antibodies cannot fight infections caused by other pathogens, so according to this framework, polio vaccines should not be able to reduce the risk associated with other viruses, such as the coronavirus.
But in the last decade, immunologists have discovered that live vaccines also stimulate the innate immune system, which is less specific but much faster. They have discovered that the innate immune system can be trained by live vaccines to better combat various types of pathogens.
For example, in a 2018 study, Dr. Netea and his colleagues vaccinated volunteers with B.C.G. or a placebo and then infected them all with a harmless version of the yellow fever virus. Those who had received B.C.G. they were better able to fight yellow fever.
Research by Dr. Netea and others shows that live vaccines train the body’s immune system by initiating changes in some stem cells. Among other things, vaccines initiate the creation of small labels that help cells activate genes involved in immune protection against multiple pathogens.
This area of innate immunity “is one of the hottest areas in fundamental immunology today,” said Dr. Robert Gallo, director of the Institute of Human Virology at the University of Maryland School of Medicine and co-founder of the Global Network. Virus, A coalition of virologists from more than 30 countries. In the 1980s, Dr. Gallo helped identify H.I.V. as the cause of AIDS.
Dr. Gallo leads the charge to test the O.P.V. Live polio vaccine as a treatment for coronavirus. He and his colleagues hope to start a clinical trial with healthcare workers in New York City and Maryland in six weeks.
O.P.V. It is commonly used in 143 countries, but is no longer found in the United States. An inactivated polio vaccine was reintroduced here in 1997, in part because one in 2.7 million people who receive the live vaccine can develop polio from it.
But O.P.V. It does not represent this risk for Americans who have received a polio vaccine in the past. “We think this is very, very, very safe,” said Dr. Gallo. It is also inexpensive at 12 cents per dose, and is administered orally, so it does not require needles.
Some scientists have raised concerns about whether these vaccines could increase the risk of “cytokine storms,” deadly inflammatory reactions that have been seen in some people weeks after becoming infected with the coronavirus. Dr. Netea and others said they were taking these concerns seriously, but did not anticipate problems. For one thing, the vaccines will be administered only to healthy people, not to people who are already infected.
Furthermore, B.C.G. it can actually increase the body’s initial immune response in a way that reduces the amount of virus in the body, so that an inflammatory response never occurs. For starters, it can “lead to less infection,” said Dr. Moshe Arditi, director of the Center for Infectious and Immune Disease Research at Cedars-Sinai Medical Center in Los Angeles, who leads one of the test arms.
The science on this is still early. Several preprints, scientific papers that have not yet been peer-reviewed, published in recent months support the idea that B.C.G. could protect against coronavirus. They have reported, for example, that death rates are lower in countries that routinely vaccinate children with B.C.G. But these studies can be loaded with biases and difficult to interpret; It is impossible to know whether vaccines, or something else, provided the protection.
Such studies are “at the bottom of the evidence hierarchy,” said Dr. Christine Stabell Benn, who is raising funds for a Danish trial at. He added that the protective effects of a dose of B.C.G administered to adults decades ago when they were infants may differ from the protective effects that the vaccine could provide when administered to adults during an outbreak.
“In the end,” said Dr. Netea, “only clinical trials will give the answer.”
Fortunately, that response will come very soon. Initial results of ongoing trials may be available in a few months. If these researchers are right, these old vaccines could save us time, and save thousands of lives, as we work to develop a new one.
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